A very useful up to date Guideline
Guideline for Management of Castration-Resistant Prostate Cancer
Author: Nick Mulcahy
CME Author: Charles P. Vega, MD, FAAFP
CME Released: 06/19/2013
This article is intended for primary care clinicians, urologists, oncologists, radiation oncologists, and other specialists who care for patients with castration-resistant prostate cancer.
There are 240,000 new diagnoses of prostate cancer in the United States annually, and most men who die of prostate cancer have metastatic castration-resistant prostate cancer (mCRPC). The median survival time of patients with mCRPC has traditionally been less than 2 years, and androgen receptors appear to remain active among these patients despite circulating levels of androgens consistent with castration.
Treatment with medications such as docetaxel has changed how CRPC is treated during the past decade. The current guideline from the American Urological Association (AUA) describes the best practice for the management of CRPC.
Study Synopsis and Perspective
The AUA has issued a new guideline for the management of CRPC that provides a "rational basis" for treatment decisions.
Those decisions are now "complex" because a group of treatment options for metastatic disease has emerged in a short period of time, according to a press release issued at AUA 2013 Annual Scientific Meeting, held in San Diego, California.
The treatment options in mCRPC include 4 new therapies that have been approved since 2010: sipuleucel-T, cabazitaxel, abiraterone, and enzalutamide. These therapies, along with docetaxel (approved in 2004), have all been shown to improve overall survival time in metastatic disease.
"Prior to 2004, once patients failed primary androgen deprivation, treatments were administered solely for palliation," write the guideline authors, led by Michael S. Cookson, MD, from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.
The guidelines are much needed, according to a clinician not involved with their writing. "There is a lack of clarity as to the best method for treating castration-resistant prostate cancer," said Willie Underwood III, MD, MPH, from the Roswell Park Cancer Institute in Buffalo, New York.
The guidance is especially important given the publicity that has accompanied the new therapies, as well as their cost, he told Medscape Medical News in an interview. "When a drug comes out with a lot of hype, every patient wants that drug."
A large part of the new guideline is recommendations for 6 different types of patients. These "index" patients represent the most common clinical scenarios in men whose prostate cancer is not responsive to traditional androgen-deprivation therapy.
The profiles of the index patients comprise symptoms, performance status, the presence or absence of metastases, and whether or not docetaxel has been administered.
The guideline authors acknowledge that treatment is rapidly changing, and advise clinicians to use it in conjunction with the "current literature" and an individual patient's treatment goals.
The following are the index patients and the associated recommendations.
Index Patient 1: Asymptomatic Nonmetastatic CRPC
Profile
The typical patient has a rising prostate-specific antigen (PSA) level and no radiologic evidence of metastatic prostate cancer. He is also required to have castrate levels of testosterone (< 50 ng/mL).
Treatment recommendations
Observation with continued androgen deprivation (preferred)
First-generation antiandrogens (flutamide, bicalutamide, and nilutamide) or first-generation androgen-synthesis inhibitors (ketoconazole plus steroid) to patients unwilling to accept observation
Discussion
No treatment has been shown to improve overall survival duration in these men. "Since all agents have potential side effects...we must first do no harm," write the authors.
Index Patient 2: Asymptomatic or Minimally Symptomatic mCRPC Without Previous Docetaxel Chemotherapy
Profile
These patients have "a rising PSA in the setting of castrate levels of testosterone" and metastatic disease documented on radiographic imaging.
Treatment recommendations
Abiraterone plus prednisone, docetaxel, or sipuleucel-T (preferred)
First-generation antiandrogen therapy or ketoconazole plus steroid or observation to patients who do not want or cannot have one of the standard therapies
Discussion
The 3 standard therapies are approved by the US Food and Drug Administration for this indication and improved overall survival time in randomized clinical trials. There are no direct comparison studies to inform optimal sequencing. "As a general principle, it is preferable to give the least toxic agent first," the authors note.
Index Patient 3: Symptomatic mCRPC With Good Performance Status and No Previous Docetaxel Chemotherapy
Profile
These patients have a rising PSA level in the setting of castrate levels of testosterone. Their symptoms should be related to prostate cancer alone (and not to other conditions) and might include pain.
Treatment recommendations
Docetaxel (preferred)
Abiraterone plus prednisone (alternative)
Ketoconazole plus steroid, mitoxantrone, or radionuclide therapy for patients who do not want or cannot have one of the standard therapies
Discussion
Sipuleucel-T immunotherapy is not recommended in symptomatic disease, the authors note.
Index Patient 4: Symptomatic mCRPC With Poor Performance Status and No Previous Docetaxel Chemotherapy
Profile
Clinical trials have generally excluded patients with a poor performance status (ECOG 3 or 4); as a result, data guiding their management are extrapolated from randomized trials of healthier patients.
Treatment recommendations
Abiraterone plus prednisone (preferred)
Ketoconazole plus steroid or radionuclide therapy to patients who are unable or unwilling to receive abiraterone plus prednisone
Docetaxel or mitoxantrone chemotherapy in select cases, specifically when performance status is directly related to the cancer
Index Patient 5: Symptomatic mCRPC With Good Performance Status and Previous Docetaxel Chemotherapy
Profile
A focus of therapy should be to maintain the excellent performance status without significant toxicity from additional therapy.
Treatment recommendations
Abiraterone plus prednisone, cabazitaxel, or enzalutamide (preferred)
If the patient received abiraterone plus prednisone before docetaxel chemotherapy, offer cabazitaxel or enzalutamide.
Ketoconazole plus steroid if abiraterone plus prednisone, cabazitaxel, or enzalutamide is unavailable
Re-treatment with docetaxel for patients who were benefiting from but discontinued treatment with docetaxel because of reversible adverse effects
Discussion
Abiraterone plus prednisone and enzalutamide appear to provide clinical benefit equivalent to (if not superior to) additional intravenous chemotherapy with an agent such as cabazitaxel. These 2 therapies have "significantly less acute toxicity and no apparent cumulative toxicity" during prolonged periods, say the authors.
Index Patient 6: Symptomatic mCRPC With Poor Performance Status and Previous Docetaxel Chemotherapy
Profile
"Treatment given in the last months of life may delay access to end-of-life care, increase costs, and add unnecessary symptom management. Patients with poor performance status (ECOG 3 or 4) should not be offered further treatment," write the authors.
Treatment recommendations
Palliative care (preferred)
For selected patients, offer treatment with abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid, or radionuclide therapy
Discussion
There is insufficient evidence demonstrating a treatment benefit in this patient population.
Because the skeletal system is the most common site for prostate cancer metastasis, the guideline also makes recommendations regarding bone health.
Bone Health
Treatment recommendations
Offer preventive treatment (eg, supplemental calcium, vitamin D) for fractures.
Choose either denosumab or zoledronic acid as preventive treatment of skeletal-related events.
"Prostate cancer deaths are typically the result of mCRPC, a painful disease," said Dr. Cookson in a press statement. "In recent years, a number of new treatments and therapeutic agents have entered the market that have been shown to minimize adverse effects and pain and prolong survival in some patients, but the fact remains that mCRPC is the terminal stage of prostate cancer."
Castration-Resistant Prostate Cancer: AUA Guideline
jueves, 30 de abril de 2015
miércoles, 29 de abril de 2015
The Precision Medicine Misconception
The Precision Medicine Misconception
Maurie Markman, MD
Published Online: Tuesday, April 28, 2015
Maurie Markman, MD. OncLive.
In the cancer research domain, the expression therapeutic misconception describes a situation in which patients mistakenly believe that the primary goal associated with their participation in a particular clinical trial is for the individual in question to attain clinical benefit. Rather, some academics and ethicists argue, the major intent of the strategy in actuality is to generate knowledge that may favorably impact the course of illness for future patients.
The aim of this commentary is not to debate the premise of this specific concept (with which this commentator strongly disagrees) but rather to highlight a different and potentially problematic therapeutic misconception now building within the oncology arena.
Amid the increasingly public discussion and often vigorous debate surrounding the general topic of precision cancer medicine, there appears to be a misconception—or one might even suggest a basic misunderstanding—of what the term is meant to imply. Some individuals seem to suggest that the term precision cancer medicine refers to a particular event or series of events whose occurrence would permit one to declare that, “The era of precision cancer medicine has arrived.”
Unfortunately, and quite similar to the profoundly flawed War on Cancer rhetoric, defining precision cancer medicine in this manner promises a biologically unattainable outcome—as in “August 17, 20xx was the day we were able to declare victory in our battle against cancer.”
When viewed in this manner, the limitations of where we are now and the flawed premise of the basic concept become clear, as medical oncologist Mikkael A. Sekeres noted recently in a commentary in The New York Times.1 For how can one objectively suggest that precision cancer medicine will “cure” any cancer—or even substantially alter the course of most malignancies—in the relatively near future?
Surely, we must acknowledge that today there are a limited number of precision cancer medicine strategies that can be described as “a home run” (eg, BRAF inhibitors in metastatic melanoma) and far fewer as a “grand slam” (eg, targeting bcr-abl fusion in chronic myeloid leukemia).
To view precision cancer medicine in this manner completely misses the point. Simply stated, precision cancer medicine is not an event or a series of events and it is certainly not a day on the calendar. Rather, precision cancer medicine is a process, a conceptually powerful way to consider the scientific development of therapeutics in both preclinical and clinical evaluation and the subsequent delivery of treatments to individual patients with cancer.
The fundamental goal of precision cancer medicine is to permit antineoplastic therapy to be more precise by targeting molecularly defined abnormalities within the cancer or demonstrated differences between a patient’s cancer versus her/his normal cellular population. For the individual patient, the successful outcome of employing the process of precision cancer medicine will be a greater probability that the delivery of a given treatment program will result in a favorable clinical result (eg, improvement in survival, time to disease progression, decease in symptoms, improved quality of life) and a corresponding reduced probability that such treatment will only lead to therapy-related side effects (and no clinical benefit), compared with current management paradigms employed in a particular setting.
This process will certainly continue to be a key component of all future antineoplastic drug discovery paradigms. For example, provocative preliminary data reveal the cancers of patients most likely to achieve clinical benefit from CTLA-4 blockade possess a high mutation load, suggesting it may be possible in the future to select a patient population more likely to achieve a favorable outcome, and less likely to experience treatment-related harm in the absence of a realistic opportunity to attain clinical benefit.2
Investigative efforts within the precision cancer medicine sphere proceed from laboratory investigative efforts or possibly observations in a related clinical setting to subsequently explore the relevance in an individual patient or group of patients. While such research will never guarantee a favorable outcome or that a new more targeted delivery strategy will become a standard of care, the search for even more precise approaches to cancer management will simply not stop.
For instance, who could say today whether early provocative data3 suggesting that measuring estrogen receptor availability following fulvestrant therapy in patients with metastatic breast cancer has a predictive value that could ultimately be incorporated into a standard of care? But if the initial experience is not confirmed in future larger studies, this unfortunate outcome does not in any manner negate the precision medicine strategy to optimize disease management.
Maurie Markman, MD
Published Online: Tuesday, April 28, 2015
Maurie Markman, MD. OncLive.
In the cancer research domain, the expression therapeutic misconception describes a situation in which patients mistakenly believe that the primary goal associated with their participation in a particular clinical trial is for the individual in question to attain clinical benefit. Rather, some academics and ethicists argue, the major intent of the strategy in actuality is to generate knowledge that may favorably impact the course of illness for future patients.
The aim of this commentary is not to debate the premise of this specific concept (with which this commentator strongly disagrees) but rather to highlight a different and potentially problematic therapeutic misconception now building within the oncology arena.
Amid the increasingly public discussion and often vigorous debate surrounding the general topic of precision cancer medicine, there appears to be a misconception—or one might even suggest a basic misunderstanding—of what the term is meant to imply. Some individuals seem to suggest that the term precision cancer medicine refers to a particular event or series of events whose occurrence would permit one to declare that, “The era of precision cancer medicine has arrived.”
Unfortunately, and quite similar to the profoundly flawed War on Cancer rhetoric, defining precision cancer medicine in this manner promises a biologically unattainable outcome—as in “August 17, 20xx was the day we were able to declare victory in our battle against cancer.”
When viewed in this manner, the limitations of where we are now and the flawed premise of the basic concept become clear, as medical oncologist Mikkael A. Sekeres noted recently in a commentary in The New York Times.1 For how can one objectively suggest that precision cancer medicine will “cure” any cancer—or even substantially alter the course of most malignancies—in the relatively near future?
Surely, we must acknowledge that today there are a limited number of precision cancer medicine strategies that can be described as “a home run” (eg, BRAF inhibitors in metastatic melanoma) and far fewer as a “grand slam” (eg, targeting bcr-abl fusion in chronic myeloid leukemia).
To view precision cancer medicine in this manner completely misses the point. Simply stated, precision cancer medicine is not an event or a series of events and it is certainly not a day on the calendar. Rather, precision cancer medicine is a process, a conceptually powerful way to consider the scientific development of therapeutics in both preclinical and clinical evaluation and the subsequent delivery of treatments to individual patients with cancer.
The fundamental goal of precision cancer medicine is to permit antineoplastic therapy to be more precise by targeting molecularly defined abnormalities within the cancer or demonstrated differences between a patient’s cancer versus her/his normal cellular population. For the individual patient, the successful outcome of employing the process of precision cancer medicine will be a greater probability that the delivery of a given treatment program will result in a favorable clinical result (eg, improvement in survival, time to disease progression, decease in symptoms, improved quality of life) and a corresponding reduced probability that such treatment will only lead to therapy-related side effects (and no clinical benefit), compared with current management paradigms employed in a particular setting.
This process will certainly continue to be a key component of all future antineoplastic drug discovery paradigms. For example, provocative preliminary data reveal the cancers of patients most likely to achieve clinical benefit from CTLA-4 blockade possess a high mutation load, suggesting it may be possible in the future to select a patient population more likely to achieve a favorable outcome, and less likely to experience treatment-related harm in the absence of a realistic opportunity to attain clinical benefit.2
Investigative efforts within the precision cancer medicine sphere proceed from laboratory investigative efforts or possibly observations in a related clinical setting to subsequently explore the relevance in an individual patient or group of patients. While such research will never guarantee a favorable outcome or that a new more targeted delivery strategy will become a standard of care, the search for even more precise approaches to cancer management will simply not stop.
For instance, who could say today whether early provocative data3 suggesting that measuring estrogen receptor availability following fulvestrant therapy in patients with metastatic breast cancer has a predictive value that could ultimately be incorporated into a standard of care? But if the initial experience is not confirmed in future larger studies, this unfortunate outcome does not in any manner negate the precision medicine strategy to optimize disease management.
Personalized Care for Liver Cancer Patients
Genomic Analyses Point to the Potential of Personalized Care for Liver Cancer Patients
By The ASCO Post
Posted: 4/28/2015 2:59:26 PM
Last Updated: 4/28/2015 2:59:26 PM
Key Points:
•Out of eight mutational signatures identified in the study, two new mutational signatures for hepatocellular carcinoma were found.
•Most patients in the study had at least one damaging alteration that could potentially be treated with either an FDA-approved drug or an investigational drug that has been studied in phase I to III clinical trials.
•Further exploring mutagenic processes through exome sequencing would improve personalized care.
A new study presented at The International Liver Congress 2015 in Vienna showed that using genomic analyses to understand how and when carcinogenic mutations occur in patients with hepatocellular carcinoma may make it possible to identify specific molecular profiles linked to tumor aggressiveness (Abstract RS-1070). These molecular profiles may help identify which patients could benefit from targeted treatment in future clinical trials.
Using exome sequencing, the investigators identified relationships between environmental exposures, such as tobacco smoke, alcohol use, and mutational patterns in hepatocellular carcinoma. The study also determined the landscape of driver genes and pathways altered in different clinical stages and etiological backgrounds. Out of eight mutational signatures identified in the study, two new mutational signatures for hepatocellular carcinoma were found.
Jessica Zucman-Rossi, MD, PhD, Director of the INSERM/University Paris Descartes Functional Genomics of Solid Tumors Laboratory explained, “Mutational signatures help with understanding the biological history of a cancer, and can enable differentiation between ongoing mutational processes and historical ones. This helps identify potential new targets for anticancer therapies.”
Study Findings
In the study, most patients had at least one damaging alteration which could potentially be treated with either a U.S. Food and Drug Administration-approved drug (28% of patients) or an investigational drug (86% of patients) which has been studied in phase I to phase III clinical trials.
“Hepatocarcinogenesis is a multistep process in which precancerous lesions can ultimately transform into liver cancer. Genomic analyses, such as exome sequencing, allow us to better understand the mutational processes involved in the development of cancers. This detailed knowledge then helps us to unravel the mutagenic processes, and to optimize personalized patient care,” said Markus Peck, MD, Secretary General, European Association for the Study of the Liver.
By The ASCO Post
Posted: 4/28/2015 2:59:26 PM
Last Updated: 4/28/2015 2:59:26 PM
Key Points:
•Out of eight mutational signatures identified in the study, two new mutational signatures for hepatocellular carcinoma were found.
•Most patients in the study had at least one damaging alteration that could potentially be treated with either an FDA-approved drug or an investigational drug that has been studied in phase I to III clinical trials.
•Further exploring mutagenic processes through exome sequencing would improve personalized care.
A new study presented at The International Liver Congress 2015 in Vienna showed that using genomic analyses to understand how and when carcinogenic mutations occur in patients with hepatocellular carcinoma may make it possible to identify specific molecular profiles linked to tumor aggressiveness (Abstract RS-1070). These molecular profiles may help identify which patients could benefit from targeted treatment in future clinical trials.
Using exome sequencing, the investigators identified relationships between environmental exposures, such as tobacco smoke, alcohol use, and mutational patterns in hepatocellular carcinoma. The study also determined the landscape of driver genes and pathways altered in different clinical stages and etiological backgrounds. Out of eight mutational signatures identified in the study, two new mutational signatures for hepatocellular carcinoma were found.
Jessica Zucman-Rossi, MD, PhD, Director of the INSERM/University Paris Descartes Functional Genomics of Solid Tumors Laboratory explained, “Mutational signatures help with understanding the biological history of a cancer, and can enable differentiation between ongoing mutational processes and historical ones. This helps identify potential new targets for anticancer therapies.”
Study Findings
In the study, most patients had at least one damaging alteration which could potentially be treated with either a U.S. Food and Drug Administration-approved drug (28% of patients) or an investigational drug (86% of patients) which has been studied in phase I to phase III clinical trials.
“Hepatocarcinogenesis is a multistep process in which precancerous lesions can ultimately transform into liver cancer. Genomic analyses, such as exome sequencing, allow us to better understand the mutational processes involved in the development of cancers. This detailed knowledge then helps us to unravel the mutagenic processes, and to optimize personalized patient care,” said Markus Peck, MD, Secretary General, European Association for the Study of the Liver.
Cancer Heterogeneity
'Big Bang' Model of Cancer Heterogeneity
Integrative approaches key to understanding cancer and developing therapies
• Date: 02 Apr 2015
• Topic: Translational research
A new commentary, published in Nature Genetics discusses integrative approach to study cancer heterogeneity. Heterogeneity is the single most important factor driving cancer progression and treatment failure, yet little is understood about how and when this heterogeneity arises. A new study shows that colorectal cancers acquire their dominant mutations early in development and that subsequent mutations, even if they confer greater fitness, are unlikely to sweep through the tumour.
Lee Moffitt Cancer Center & Research Institute researchers are using integrative approaches to study cancer by combining mathematical and computational modeling with experimental and clinical data. The use of integrative approaches enables scientists to study and model cancer progression in a manner that conventional experimental systems are unable to do.
Alexander Anderson, PhD, chair of the Department of Integrated Mathematical Oncology and Mark Robertson-Tessi, an applied research scientist in the same department, recently published a commentary on an integrative approach used to study cancer heterogeneity.
Cancer is a heterogeneous disease, with genetic variations occurring between different types of tumours and different patients. More importantly, heterogeneity also exists among the cells of a single tumour. This heterogeneity makes treating cancer extremely difficult and can also lead to resistance to therapeutic agents.
Anderson and Robertson-Tessi explained that in order to develop better therapeutic approaches, it is important for scientists to identify these variations and how they lead to tumour growth and invasion. They described a new theory called the "Big Bang" model of cancer heterogeneity, developed by researchers from the University of Southern California.
The traditional model of tumour heterogeneity suggests that sequential mutations over time lead to the emergence of fitter cells that continue to grow and take over the tumour – called the clonal selection model. Contrary, the Big Bang model suggests that for some tumours, mutations occur early during development when tumours are smaller. This type of heterogeneity is common in tumours that are not limited by space and have a lot of room to grow and expand, as exemplified by colorectal cancer.
According to the Moffitt scientists, this paradigm shift may have significant implications for treatments for cancer that develop similar to colorectal cancer. Following cancer therapy, the dominant cells may die first, and other cells that were originally not as fit may find themselves better able to compete for necessary space and nutrients and continue to grow and take over the tumour.
"Understanding how heterogeneity changes with treatment is key to controlling the emergence of aggressive and resistant clones following therapy," explained Anderson. However, current therapeutic approaches that treat a tumour until resistance develops, ignore the fact that tumours can change during treatment.
The integrated approaches being developed and used at Moffitt are instrumental for the continued advancement in the understanding of cancer progression and the development of novel cancer therapies.
Reference
Robertson-Tessi M, Anderson ARA. Big Bang and context-driven collapse. Nature Genetics 2015; 47, 196–197. doi:10.1038/ng.3231
Integrative approaches key to understanding cancer and developing therapies
• Date: 02 Apr 2015
• Topic: Translational research
A new commentary, published in Nature Genetics discusses integrative approach to study cancer heterogeneity. Heterogeneity is the single most important factor driving cancer progression and treatment failure, yet little is understood about how and when this heterogeneity arises. A new study shows that colorectal cancers acquire their dominant mutations early in development and that subsequent mutations, even if they confer greater fitness, are unlikely to sweep through the tumour.
Lee Moffitt Cancer Center & Research Institute researchers are using integrative approaches to study cancer by combining mathematical and computational modeling with experimental and clinical data. The use of integrative approaches enables scientists to study and model cancer progression in a manner that conventional experimental systems are unable to do.
Alexander Anderson, PhD, chair of the Department of Integrated Mathematical Oncology and Mark Robertson-Tessi, an applied research scientist in the same department, recently published a commentary on an integrative approach used to study cancer heterogeneity.
Cancer is a heterogeneous disease, with genetic variations occurring between different types of tumours and different patients. More importantly, heterogeneity also exists among the cells of a single tumour. This heterogeneity makes treating cancer extremely difficult and can also lead to resistance to therapeutic agents.
Anderson and Robertson-Tessi explained that in order to develop better therapeutic approaches, it is important for scientists to identify these variations and how they lead to tumour growth and invasion. They described a new theory called the "Big Bang" model of cancer heterogeneity, developed by researchers from the University of Southern California.
The traditional model of tumour heterogeneity suggests that sequential mutations over time lead to the emergence of fitter cells that continue to grow and take over the tumour – called the clonal selection model. Contrary, the Big Bang model suggests that for some tumours, mutations occur early during development when tumours are smaller. This type of heterogeneity is common in tumours that are not limited by space and have a lot of room to grow and expand, as exemplified by colorectal cancer.
According to the Moffitt scientists, this paradigm shift may have significant implications for treatments for cancer that develop similar to colorectal cancer. Following cancer therapy, the dominant cells may die first, and other cells that were originally not as fit may find themselves better able to compete for necessary space and nutrients and continue to grow and take over the tumour.
"Understanding how heterogeneity changes with treatment is key to controlling the emergence of aggressive and resistant clones following therapy," explained Anderson. However, current therapeutic approaches that treat a tumour until resistance develops, ignore the fact that tumours can change during treatment.
The integrated approaches being developed and used at Moffitt are instrumental for the continued advancement in the understanding of cancer progression and the development of novel cancer therapies.
Reference
Robertson-Tessi M, Anderson ARA. Big Bang and context-driven collapse. Nature Genetics 2015; 47, 196–197. doi:10.1038/ng.3231
martes, 28 de abril de 2015
There is no ‘safe’ cigarette
ELCC 2015 Press Release
Smokers Underestimate Risks of a Few Cigarettes
Survey shows that many live in ‘denial’ of the real risks of smoking even a small number of cigarettes a day
Date: 17 Apr 2015
Topic: Epidemiology/Etiology/Cancer Prevention / Lung and other thoracic tumours
Geneva, Switzerland-- Many people still dangerously underestimate the health risks associated with smoking even a few cigarettes a day, despite decades of public health campaigning, French researchers have reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.
The results demonstrate powerfully that the war against smoking is far from over, says oncologist Dr Laurent Greillier from Hopital Nord in Marseille, France, who presented the results at the conference.
Greillier and colleagues analysed data from a representative survey of 1602 French people aged between 40 and 75 years. This ‘Edifice’ survey included 1463 people with no history of cancer, of whom 481 were former smokers and 330 were current smokers, with an average daily consumption of 14.2 cigarettes.
“Nowadays everyone knows that smoking is a risk factor for developing several cancers, especially lung cancer,” Greillier explained. “In this new survey we hypothesized that the perception of the risk of developing this disease could be influenced by personal smoking history. In other words, we thought that the risk might be minimised in smokers compared with never-smokers.”
Among the whole sample population, 34% wrongly considered that a daily consumption of up to 10 cigarettes was not associated with any risk of lung cancer, Greillier reported. “This finding is particularly impressive and threatening. It shows that relatively low cigarette consumption is considered as ‘safe’ for a lot of people. In our study, only half of subjects answered that there is no ‘safe’ cigarette.”
Only half of current smokers considered themselves at higher risk of lung cancer than the average-risk population, and less than 40% of individuals were aware that the risk of lung cancer never disappears after smoking cessation.
“It seems that people are aware about the dangers of tobacco for health, but might consider that the risks are not for themselves, but only for other people,” Greillier said.
“It is essential that public health policies continue to focus on the tobacco pandemic. Our findings suggest to urgently initiating campaigns concerning the risk of any cigarette. The war against tobacco is not over!”
Commenting on the study, Dr Carolyn Dresler, a US-based Board Member of the International Association for the Study of Lung Cancer (IASLC), said that the results reflect a common situation internationally.
“People who smoke very much tend to underestimate their risks,” Dresler said, “and it makes me think that ‘denial’ is still prevalent. As an oncologist and tobacco control advocate, it amazes me and strikes me as so unfortunate that such lack of knowledge is so prevalent.”
“The risk for lung cancer is most dependent on duration of smoking, but of course the number per day matters also,” Dresler said. “The risk for cardiovascular disease starts with that one cigarette per day. So, this survey demonstrates that MUCH education is still required.”
“It is very important to make sure that accurate information about the actual risks of tobacco use, particularly for those who continue to smoke, is disseminated,” Dresler concluded. “We all have a strong ‘denial gene’ in us, and education must be clear, relevant and repeated if we are to change the perceptions that are evident from this survey.”
-END-
Notes to Editors
Abs. 21PD_PR Perception of lung cancer (LC) risk: Impact of smoking status and nicotine dependence. L. Greillier, FR
To be presented at ELCC 2015 on Friday 17.04.2015 from 14:30 to 15:45 Poster Discussion
Smokers Underestimate Risks of a Few Cigarettes
Survey shows that many live in ‘denial’ of the real risks of smoking even a small number of cigarettes a day
Date: 17 Apr 2015
Topic: Epidemiology/Etiology/Cancer Prevention / Lung and other thoracic tumours
Geneva, Switzerland-- Many people still dangerously underestimate the health risks associated with smoking even a few cigarettes a day, despite decades of public health campaigning, French researchers have reported at the European Lung Cancer Conference (ELCC) in Geneva, Switzerland.
The results demonstrate powerfully that the war against smoking is far from over, says oncologist Dr Laurent Greillier from Hopital Nord in Marseille, France, who presented the results at the conference.
Greillier and colleagues analysed data from a representative survey of 1602 French people aged between 40 and 75 years. This ‘Edifice’ survey included 1463 people with no history of cancer, of whom 481 were former smokers and 330 were current smokers, with an average daily consumption of 14.2 cigarettes.
“Nowadays everyone knows that smoking is a risk factor for developing several cancers, especially lung cancer,” Greillier explained. “In this new survey we hypothesized that the perception of the risk of developing this disease could be influenced by personal smoking history. In other words, we thought that the risk might be minimised in smokers compared with never-smokers.”
Among the whole sample population, 34% wrongly considered that a daily consumption of up to 10 cigarettes was not associated with any risk of lung cancer, Greillier reported. “This finding is particularly impressive and threatening. It shows that relatively low cigarette consumption is considered as ‘safe’ for a lot of people. In our study, only half of subjects answered that there is no ‘safe’ cigarette.”
Only half of current smokers considered themselves at higher risk of lung cancer than the average-risk population, and less than 40% of individuals were aware that the risk of lung cancer never disappears after smoking cessation.
“It seems that people are aware about the dangers of tobacco for health, but might consider that the risks are not for themselves, but only for other people,” Greillier said.
“It is essential that public health policies continue to focus on the tobacco pandemic. Our findings suggest to urgently initiating campaigns concerning the risk of any cigarette. The war against tobacco is not over!”
Commenting on the study, Dr Carolyn Dresler, a US-based Board Member of the International Association for the Study of Lung Cancer (IASLC), said that the results reflect a common situation internationally.
“People who smoke very much tend to underestimate their risks,” Dresler said, “and it makes me think that ‘denial’ is still prevalent. As an oncologist and tobacco control advocate, it amazes me and strikes me as so unfortunate that such lack of knowledge is so prevalent.”
“The risk for lung cancer is most dependent on duration of smoking, but of course the number per day matters also,” Dresler said. “The risk for cardiovascular disease starts with that one cigarette per day. So, this survey demonstrates that MUCH education is still required.”
“It is very important to make sure that accurate information about the actual risks of tobacco use, particularly for those who continue to smoke, is disseminated,” Dresler concluded. “We all have a strong ‘denial gene’ in us, and education must be clear, relevant and repeated if we are to change the perceptions that are evident from this survey.”
-END-
Notes to Editors
Abs. 21PD_PR Perception of lung cancer (LC) risk: Impact of smoking status and nicotine dependence. L. Greillier, FR
To be presented at ELCC 2015 on Friday 17.04.2015 from 14:30 to 15:45 Poster Discussion
The high cost of new cancer drugs
ASCO Post
In Search of ‘Just’ Prices: Questioning the High Cost of New Cancer Drugs
A Conversation With Hagop M. Kantarjian, MD
By Ronald Piana
April 25, 2015, Volume 6, Issue 7
Hagop M. Kantarjian, MD
As the oncology community begins the slow and often difficult-to-define transition from volume to value in the delivery of cancer care, the relationship between the price and value of certain high-priced cancer drugs is getting more scrutiny. We generally correlate the efficacy of a new drug and its price by complicated cost-efficacy ratios or quality-adjusted life-years. To shed light on this important issue, The ASCO Post recently spoke with nationally regarded leukemia expert Hagop M. Kantarjian, MD, Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Defining Benefit
In our cost-constrained health-care system, what counts as a benefit in cancer treatment?
Even as we are looking at treatment value, it is important to note that in most cancers we are far from curing patients with effective and optimal therapies that produce maximum efficacy with minimal toxicity. Therefore, I would consider a benefit in cancer treatment as any metric that improves survival or other parameters important to the patient, such as improved well-being and quality-of-life measures.
We should not restrict our evaluation of benefit to one parameter. It needs to be an across-the-board assessment of multiple clinical endpoints that determine the treatment’s overall contribution to the condition of the patient.
Cost and Decision-Making
How much should cost of oncologic agents factor into a physician’s treatment decisions?
The data show that cancer patients want their oncologists to make treatment decisions based on the most effective treatment, regardless of the price. Everyone understands that the rising costs of cancer treatments contribute to the fiscal dangers faced by our health-care system. But in the intimate doctor-patient setting, it’s all about delivering the best care to our vulnerable cancer patients.
Cost discussions should be reserved for the larger public forum. It is an essential public health debate, because currently there is little correlation between the actual cost of a cancer drug and its price.
Free-Market Pricing
A growing number of oncologists have been questioning the high costs of new cancer drugs. What’s your opinion on this difficult issue of pricing in a free-market system?
In many cases, pharmaceutical companies make excessive profits on the cancer drugs marketed in the United States. For example, U.S. drug companies make very good margins in Europe and elsewhere, despite the fact that most countries outside the United States have government- and other entity-sponsored negotiations to reduce and control the price of cancer drugs. We have no such price controls in the United States.
At the recent American Society of Hematology (ASH) meeting, an expert contended that the cost for cancer drugs outside the United States is only 30% lower than in the United States. This is a misleading data point, because it conflates the prices of both patented and generic drugs. Outside the United States, generic drugs are indeed more expensive because they don’t use the average sales price-plus-6% formula in their cost valuation. No matter how you spin the data, U.S. cancer patients pay 50% to 300% more for patented cancer drugs than cancer patients in Europe and other regions.
Furthermore, many of the patented cancer drugs entering the U.S. market are priced at more than $100,000 per year. In my opinion, no cancer drug should cost more than $40,000 per year. That would be an equitable price for a drug that prolongs life for 1 year and would offer the drug company reasonable profits without crossing the line into profiteering from an unjust price.
The current drugs that cost more than $100,000 are priced in excess of their value, and this unwarranted pricing trend is harming our patients and causing personal and social injustice. Depending on the value in survival and/or quality of life, cancer drugs should be priced from about $10,000 to $40,000.
Research and Development Costs
Pharmaceutical companies routinely justify the high costs of their drugs as necessary to defray the large investment in research and development (R&D). Do you feel that explanation accurately explains the costs of new cancer therapies?
I believe that the R&D outlay as it relates to drug costs is misinformation. Many companies have used $1 billion as their cost to bring a drug from the lab to the market; however, many pharmaceutical company CEOs are now backtracking from that extraordinary number because it includes, among other things, 11% compounded interest annually for 15 years.
It also includes government rebates for such things as orphan drugs, and it cites the mean cost of developing the drug as opposed to the median, which increases the cost by another 30%. I’ve studied and written on this subject, and I’d venture that the cost of R&D is about 10% of what numerous companies cite.
Instead of justifying high costs of drugs because of R&D expenses, companies should be exploring ways to reduce their R&D costs, such as developing more intelligent trial designs, having discussions with the U.S. Food and Drug Administration (FDA) about reducing unnecessary administrative work, and other factors that slow the process and add superfluous costs. There are many ways to reduce cost that won’t compromise the quality of the drug development process.
Bar for Approval
Many of the new biologics have been approved based on endpoints other than overall survival, such as objective response or progression-free survival. Some argue that these endpoints allow drugs with little true benefit for survival or symptom relief to reach the market; therefore, we should raise the bar for approval. What is your opinion on this issue?
I would argue the opposite; I think we should lower the approval bar and get more drugs to the market. For example, in acute myeloid leukemia (AML), because the approval bar has been raised so high, the FDA has not approved a single drug for AML in more than 3 decades.
I believe that overall survival should not be the only endpoint for approval. We should consider event-free survival, response rate, quality-of-life parameters, and other factors. We should have as many FDA-approved agents on the market as possible, because once drugs are approved, they are available to outside investigators to explore using the drugs in different combinations and other tumors, which could lead to discoveries that were missed by the original researchers.
Out-of-Pocket Expenses
Medical debt is a growing problem in today’s health-care environment. Out-of-pocket copays for expensive cancer drugs are a real challenge for many patients. Is there a way to challenge the status quo that sets the prices of cancer drugs?
As mentioned, most of the new drugs being approved cost more than $100,000 per year, so out-of-pocket copay expenses for, say, the average family income of $48,000 is a crushing financial burden. If you look at seniors, whose average annual income is about $32,000, their copays for cancer drugs have driven many into bankruptcy. In short, out-of-pocket expenses for cancer care are preventing some patients from accessing care and harming many others.
In my opinion, we should vigorously find ways to totally eliminate out-of-pocket expenses for cancer patients. This isn’t a unique idea. For example, in my home country of Lebanon, cancer care is delivered without any out-of-pocket expenses. If patients can’t pay for the drugs, the government foots the bill. I think in the United States, we should find a way to achieve zero out-of-pocket expenses for patented cancer drugs.
Social Responsibility
Any last thoughts on drug pricing?
It’s not as complicated an issue as it might seem. But as a growing number of oncologists voice concern about the costs of cancer drugs, we’ll see a public relations campaign by the pharmaceutical industry to justify the prices of these drugs. The central argument is that if they are constrained in pricing, it will stifle valuable innovation. The reality is that since 2000, the pharmaceutical industry has discarded their social responsibility to provide cancer therapies at a just pricing level that patients can afford.
Nobody is against reasonable profit, but since the Medicare Modernization Act of 2003 and the legislation of Medicare Part D, which made drug companies the sole arbiter on pricing, we’ve seen an alarming increase in drug prices that is harming our patients and our health-care system. As physicians guided by the Hippocratic oath, it is up to us to stand up for our patients and counter the people and institutions that have a vested interest in keeping cancer drugs priced at an artificially inflated rate. As doctors, we should be strong advocates for our patients. ■
Disclosure: Dr. Kantarjian reported no potential conflicts of interest.
In Search of ‘Just’ Prices: Questioning the High Cost of New Cancer Drugs
A Conversation With Hagop M. Kantarjian, MD
By Ronald Piana
April 25, 2015, Volume 6, Issue 7
Hagop M. Kantarjian, MD
As the oncology community begins the slow and often difficult-to-define transition from volume to value in the delivery of cancer care, the relationship between the price and value of certain high-priced cancer drugs is getting more scrutiny. We generally correlate the efficacy of a new drug and its price by complicated cost-efficacy ratios or quality-adjusted life-years. To shed light on this important issue, The ASCO Post recently spoke with nationally regarded leukemia expert Hagop M. Kantarjian, MD, Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
Defining Benefit
In our cost-constrained health-care system, what counts as a benefit in cancer treatment?
Even as we are looking at treatment value, it is important to note that in most cancers we are far from curing patients with effective and optimal therapies that produce maximum efficacy with minimal toxicity. Therefore, I would consider a benefit in cancer treatment as any metric that improves survival or other parameters important to the patient, such as improved well-being and quality-of-life measures.
We should not restrict our evaluation of benefit to one parameter. It needs to be an across-the-board assessment of multiple clinical endpoints that determine the treatment’s overall contribution to the condition of the patient.
Cost and Decision-Making
How much should cost of oncologic agents factor into a physician’s treatment decisions?
The data show that cancer patients want their oncologists to make treatment decisions based on the most effective treatment, regardless of the price. Everyone understands that the rising costs of cancer treatments contribute to the fiscal dangers faced by our health-care system. But in the intimate doctor-patient setting, it’s all about delivering the best care to our vulnerable cancer patients.
Cost discussions should be reserved for the larger public forum. It is an essential public health debate, because currently there is little correlation between the actual cost of a cancer drug and its price.
Free-Market Pricing
A growing number of oncologists have been questioning the high costs of new cancer drugs. What’s your opinion on this difficult issue of pricing in a free-market system?
In many cases, pharmaceutical companies make excessive profits on the cancer drugs marketed in the United States. For example, U.S. drug companies make very good margins in Europe and elsewhere, despite the fact that most countries outside the United States have government- and other entity-sponsored negotiations to reduce and control the price of cancer drugs. We have no such price controls in the United States.
At the recent American Society of Hematology (ASH) meeting, an expert contended that the cost for cancer drugs outside the United States is only 30% lower than in the United States. This is a misleading data point, because it conflates the prices of both patented and generic drugs. Outside the United States, generic drugs are indeed more expensive because they don’t use the average sales price-plus-6% formula in their cost valuation. No matter how you spin the data, U.S. cancer patients pay 50% to 300% more for patented cancer drugs than cancer patients in Europe and other regions.
Furthermore, many of the patented cancer drugs entering the U.S. market are priced at more than $100,000 per year. In my opinion, no cancer drug should cost more than $40,000 per year. That would be an equitable price for a drug that prolongs life for 1 year and would offer the drug company reasonable profits without crossing the line into profiteering from an unjust price.
The current drugs that cost more than $100,000 are priced in excess of their value, and this unwarranted pricing trend is harming our patients and causing personal and social injustice. Depending on the value in survival and/or quality of life, cancer drugs should be priced from about $10,000 to $40,000.
Research and Development Costs
Pharmaceutical companies routinely justify the high costs of their drugs as necessary to defray the large investment in research and development (R&D). Do you feel that explanation accurately explains the costs of new cancer therapies?
I believe that the R&D outlay as it relates to drug costs is misinformation. Many companies have used $1 billion as their cost to bring a drug from the lab to the market; however, many pharmaceutical company CEOs are now backtracking from that extraordinary number because it includes, among other things, 11% compounded interest annually for 15 years.
It also includes government rebates for such things as orphan drugs, and it cites the mean cost of developing the drug as opposed to the median, which increases the cost by another 30%. I’ve studied and written on this subject, and I’d venture that the cost of R&D is about 10% of what numerous companies cite.
Instead of justifying high costs of drugs because of R&D expenses, companies should be exploring ways to reduce their R&D costs, such as developing more intelligent trial designs, having discussions with the U.S. Food and Drug Administration (FDA) about reducing unnecessary administrative work, and other factors that slow the process and add superfluous costs. There are many ways to reduce cost that won’t compromise the quality of the drug development process.
Bar for Approval
Many of the new biologics have been approved based on endpoints other than overall survival, such as objective response or progression-free survival. Some argue that these endpoints allow drugs with little true benefit for survival or symptom relief to reach the market; therefore, we should raise the bar for approval. What is your opinion on this issue?
I would argue the opposite; I think we should lower the approval bar and get more drugs to the market. For example, in acute myeloid leukemia (AML), because the approval bar has been raised so high, the FDA has not approved a single drug for AML in more than 3 decades.
I believe that overall survival should not be the only endpoint for approval. We should consider event-free survival, response rate, quality-of-life parameters, and other factors. We should have as many FDA-approved agents on the market as possible, because once drugs are approved, they are available to outside investigators to explore using the drugs in different combinations and other tumors, which could lead to discoveries that were missed by the original researchers.
Out-of-Pocket Expenses
Medical debt is a growing problem in today’s health-care environment. Out-of-pocket copays for expensive cancer drugs are a real challenge for many patients. Is there a way to challenge the status quo that sets the prices of cancer drugs?
As mentioned, most of the new drugs being approved cost more than $100,000 per year, so out-of-pocket copay expenses for, say, the average family income of $48,000 is a crushing financial burden. If you look at seniors, whose average annual income is about $32,000, their copays for cancer drugs have driven many into bankruptcy. In short, out-of-pocket expenses for cancer care are preventing some patients from accessing care and harming many others.
In my opinion, we should vigorously find ways to totally eliminate out-of-pocket expenses for cancer patients. This isn’t a unique idea. For example, in my home country of Lebanon, cancer care is delivered without any out-of-pocket expenses. If patients can’t pay for the drugs, the government foots the bill. I think in the United States, we should find a way to achieve zero out-of-pocket expenses for patented cancer drugs.
Social Responsibility
Any last thoughts on drug pricing?
It’s not as complicated an issue as it might seem. But as a growing number of oncologists voice concern about the costs of cancer drugs, we’ll see a public relations campaign by the pharmaceutical industry to justify the prices of these drugs. The central argument is that if they are constrained in pricing, it will stifle valuable innovation. The reality is that since 2000, the pharmaceutical industry has discarded their social responsibility to provide cancer therapies at a just pricing level that patients can afford.
Nobody is against reasonable profit, but since the Medicare Modernization Act of 2003 and the legislation of Medicare Part D, which made drug companies the sole arbiter on pricing, we’ve seen an alarming increase in drug prices that is harming our patients and our health-care system. As physicians guided by the Hippocratic oath, it is up to us to stand up for our patients and counter the people and institutions that have a vested interest in keeping cancer drugs priced at an artificially inflated rate. As doctors, we should be strong advocates for our patients. ■
Disclosure: Dr. Kantarjian reported no potential conflicts of interest.
lunes, 27 de abril de 2015
First joint guideline issued by Radiation Therapists and Urologists
Essential update: First joint guideline on prostate cancer therapy issued by ASTRO and AUA Medscape
For the first time in their history, the 2 medical organizations most responsible for the treatment of prostate cancer in the United States—the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA)—have issued a joint guideline, a series of 9 major statements on the use of radiation therapy (either adjuvant or salvage) after prostatectomy. The statements are categorized as follows[1, 2] :
Clinical principles - Wide agreement by urologists
Recommendations - Grade C; low-quality and certainty evidence
Standards - Grade A or B; high/moderate-quality and certainty evidence
Options – Nondirectives
The guideline statements are as follows:
If a patient is undergoing radical prostatectomy for localized prostate cancer, discuss the possibility of adverse pathologic findings indicating an increased cancer recurrence risk (clinical principle)
If adverse pathologic signs—such as seminal vesicle invasion, positive surgical margins, and extraprostatic extension—are found, inform the patient that the risk for biochemical (prostate-specific antigen [PSA]) recurrence, local recurrence, or clinical progression of cancer is lower following a combination of radical prostatectomy and adjuvant radiation therapy than it is after radical prostatectomy alone (clinical principle)
If adverse pathologic signs are found at prostatectomy, offer adjuvant radiation therapy to the patient (standard; evidence strength, grade A)
Inform patients that PSA recurrence after surgery is associated with a higher risk for metastatic prostate cancer and with an increased mortality risk (clinical principle)
Biochemical recurrence should be defined as a detectable or rising postsurgery PSA value of at least 0.2 ng/mL, with a second confirmatory level of at least 0.2 ng/mL (recommendation; evidence strength, grade C)
A restaging evaluation should be considered in patients with a PSA recurrence (option; evidence strength, grade C)
Offer salvage radiation therapy to patients who, after radical prostatectomy, demonstrate PSA or local recurrence but have no distant metastatic disease (recommendation; evidence strength, grade C)
Inform patients that radiation therapy is most effective against PSA recurrence when PSA levels are relatively low (clinical principle).
Inform patients that radiation therapy may cause short- or long-term urinary, bowel, and sexual adverse effects, but also discuss the treatment’s potential benefits as a means of controlling disease recurrence (clinical principle).
Conventional EBRT
Conventional EBRT is typically delivered by means of a 4-field technique. The 4 fields (anteroposterior [AP], posteroanterior [PA], left lateral, and right lateral) are designed to include the prostate, the seminal vesicles, and the regional lymphatic vessels.
The morbidity of radiation treatment is intimately linked to the volume of normal tissue treated. Conventional radiotherapy includes irradiation of large volumes of tissue, including the skin, small bowel, bladder, large bowel, pelvic bones, and additional areas of soft tissue.
3-Dimensional conformal radiotherapy
In 3-dimensional conformal radiotherapy (3D-CRT), the radiation beam is shaped to include the 3D anatomic configuration of the prostate and any specified adjacent tissue (including the seminal vesicles and periprostatic adventitial tissues). This technique allows more precise delivery of therapy to the target organ or organs.
Intensity-modulated radiation therapy
Intensity-modulated radiation therapy (IMRT) can achieve tightly conformal dose distributions with the use of nonuniform radiation beams. The intent of this form of therapy is to create highly conformal fields by treating the patient with multiple static portals (so-called step-and-shoot IMRT) or dynamic fields. In dynamic IMRT, a series of arcs are administered through the area of interest. Multileaf collimators (MLCs) are reshaped many times as the machine performs a series of arc rotations around the target.
Image-guided radiotherapy
The term image-guided radiotherapy (IGRT) refers to the use of imaging techniques, including the following, in an attempt to ensure proper target localization during the course of radiotherapy:
Interfractional assessment (static) [3]
Portal imaging - The implantation of radiopaque fiducial markers into the prostatic target allows a soft tissue target to be localized with portal imaging technology
Ultrasonography - Ultrasonographic images of the prostate are obtained on a daily basis to identify the gland’s relative position
Computed tomography (CT) scanning - The radiation used for therapy can also be used to generate a CT image [4]
Radiofrequency localization - Small radio transponders can be implanted in the prostate to facilitate patient setup
Proton beam therapy
In contrast to photon beam therapy, the entrance radiation dose in proton beam therapy tends to be significantly less than the maximum energy of the clinical beam. Proton beams have a characteristic Bragg peak. Beyond this point, where energy is at a maximum intensity level, radiation energy rapidly falls off, which is important in the management of normal tissue toxicity.
Tomotherapy
Tomotherapy consists of helical radiotherapy using a computed tomography (CT)-like gantry and a rotating radiation beam that passes through the target area of interest; this modality has been used in the management of primary central nervous system tumors and viscera-based malignancies.
Hypofractionated radiotherapy
In this form of therapy, radiation is delivered from an accelerator, with the equipment mounted to a computer-guided robotic arm; because the machine is capable of treating the target at angles that are not possible with conventional rotation-based equipment, it yields the theoretical advantage of conforming the dose more closely to the target organ’s shape
Radiotherapy and androgen ablation
Data from the Radiation Therapy Oncology Group (RTOG) have shown a clear improvement in biochemical control of disease when patients receive a combination of radiotherapy and androgen-suppressive treatment. The results of several phase III clinical trials suggest that the true benefit of combining radiotherapy with androgen blockade may lie in the potentially synergistic effects of the 2 treatments.
Adjunctive EBRT
Combined prostate implantation and EBRT
A comprehensive literature review indicated that for high-risk patients, combination therapies involving EBRT and brachytherapy with or without androgen deprivation therapy appear to be superior to more localized treatments, such as seed implant alone, surgery alone, or EBRT.[5]
EBRT after radical prostatectomy
Multi-institutional data from the American Society of Therapeutic Radiation Oncology (ASTRO) consensus conference suggest that in patients treated for a rising PSA level, postoperative radiotherapy (typically in a dose range of 60-65 Gy) offers a PSA remission rate of 70%. Unfortunately, the durability of this response varies widely from center to center, with averages ranging from 25 to 67 months.
For the first time in their history, the 2 medical organizations most responsible for the treatment of prostate cancer in the United States—the American Society for Radiation Oncology (ASTRO) and the American Urological Association (AUA)—have issued a joint guideline, a series of 9 major statements on the use of radiation therapy (either adjuvant or salvage) after prostatectomy. The statements are categorized as follows[1, 2] :
Clinical principles - Wide agreement by urologists
Recommendations - Grade C; low-quality and certainty evidence
Standards - Grade A or B; high/moderate-quality and certainty evidence
Options – Nondirectives
The guideline statements are as follows:
If a patient is undergoing radical prostatectomy for localized prostate cancer, discuss the possibility of adverse pathologic findings indicating an increased cancer recurrence risk (clinical principle)
If adverse pathologic signs—such as seminal vesicle invasion, positive surgical margins, and extraprostatic extension—are found, inform the patient that the risk for biochemical (prostate-specific antigen [PSA]) recurrence, local recurrence, or clinical progression of cancer is lower following a combination of radical prostatectomy and adjuvant radiation therapy than it is after radical prostatectomy alone (clinical principle)
If adverse pathologic signs are found at prostatectomy, offer adjuvant radiation therapy to the patient (standard; evidence strength, grade A)
Inform patients that PSA recurrence after surgery is associated with a higher risk for metastatic prostate cancer and with an increased mortality risk (clinical principle)
Biochemical recurrence should be defined as a detectable or rising postsurgery PSA value of at least 0.2 ng/mL, with a second confirmatory level of at least 0.2 ng/mL (recommendation; evidence strength, grade C)
A restaging evaluation should be considered in patients with a PSA recurrence (option; evidence strength, grade C)
Offer salvage radiation therapy to patients who, after radical prostatectomy, demonstrate PSA or local recurrence but have no distant metastatic disease (recommendation; evidence strength, grade C)
Inform patients that radiation therapy is most effective against PSA recurrence when PSA levels are relatively low (clinical principle).
Inform patients that radiation therapy may cause short- or long-term urinary, bowel, and sexual adverse effects, but also discuss the treatment’s potential benefits as a means of controlling disease recurrence (clinical principle).
Conventional EBRT
Conventional EBRT is typically delivered by means of a 4-field technique. The 4 fields (anteroposterior [AP], posteroanterior [PA], left lateral, and right lateral) are designed to include the prostate, the seminal vesicles, and the regional lymphatic vessels.
The morbidity of radiation treatment is intimately linked to the volume of normal tissue treated. Conventional radiotherapy includes irradiation of large volumes of tissue, including the skin, small bowel, bladder, large bowel, pelvic bones, and additional areas of soft tissue.
3-Dimensional conformal radiotherapy
In 3-dimensional conformal radiotherapy (3D-CRT), the radiation beam is shaped to include the 3D anatomic configuration of the prostate and any specified adjacent tissue (including the seminal vesicles and periprostatic adventitial tissues). This technique allows more precise delivery of therapy to the target organ or organs.
Intensity-modulated radiation therapy
Intensity-modulated radiation therapy (IMRT) can achieve tightly conformal dose distributions with the use of nonuniform radiation beams. The intent of this form of therapy is to create highly conformal fields by treating the patient with multiple static portals (so-called step-and-shoot IMRT) or dynamic fields. In dynamic IMRT, a series of arcs are administered through the area of interest. Multileaf collimators (MLCs) are reshaped many times as the machine performs a series of arc rotations around the target.
Image-guided radiotherapy
The term image-guided radiotherapy (IGRT) refers to the use of imaging techniques, including the following, in an attempt to ensure proper target localization during the course of radiotherapy:
Interfractional assessment (static) [3]
Portal imaging - The implantation of radiopaque fiducial markers into the prostatic target allows a soft tissue target to be localized with portal imaging technology
Ultrasonography - Ultrasonographic images of the prostate are obtained on a daily basis to identify the gland’s relative position
Computed tomography (CT) scanning - The radiation used for therapy can also be used to generate a CT image [4]
Radiofrequency localization - Small radio transponders can be implanted in the prostate to facilitate patient setup
Proton beam therapy
In contrast to photon beam therapy, the entrance radiation dose in proton beam therapy tends to be significantly less than the maximum energy of the clinical beam. Proton beams have a characteristic Bragg peak. Beyond this point, where energy is at a maximum intensity level, radiation energy rapidly falls off, which is important in the management of normal tissue toxicity.
Tomotherapy
Tomotherapy consists of helical radiotherapy using a computed tomography (CT)-like gantry and a rotating radiation beam that passes through the target area of interest; this modality has been used in the management of primary central nervous system tumors and viscera-based malignancies.
Hypofractionated radiotherapy
In this form of therapy, radiation is delivered from an accelerator, with the equipment mounted to a computer-guided robotic arm; because the machine is capable of treating the target at angles that are not possible with conventional rotation-based equipment, it yields the theoretical advantage of conforming the dose more closely to the target organ’s shape
Radiotherapy and androgen ablation
Data from the Radiation Therapy Oncology Group (RTOG) have shown a clear improvement in biochemical control of disease when patients receive a combination of radiotherapy and androgen-suppressive treatment. The results of several phase III clinical trials suggest that the true benefit of combining radiotherapy with androgen blockade may lie in the potentially synergistic effects of the 2 treatments.
Adjunctive EBRT
Combined prostate implantation and EBRT
A comprehensive literature review indicated that for high-risk patients, combination therapies involving EBRT and brachytherapy with or without androgen deprivation therapy appear to be superior to more localized treatments, such as seed implant alone, surgery alone, or EBRT.[5]
EBRT after radical prostatectomy
Multi-institutional data from the American Society of Therapeutic Radiation Oncology (ASTRO) consensus conference suggest that in patients treated for a rising PSA level, postoperative radiotherapy (typically in a dose range of 60-65 Gy) offers a PSA remission rate of 70%. Unfortunately, the durability of this response varies widely from center to center, with averages ranging from 25 to 67 months.
sábado, 25 de abril de 2015
cancer genomics and genomics research
AACR cancer progress report.
Nikhil Wagle, MD
Instructor in Medicine at the Dana-Farber Cancer Institute, Boston, and Associate Member of the Broad Institute, Cambridge, Massachusetts.
There's been a revolution in cancer genomics and genomics research over the past decade, thanks to the plummeting cost of sequencing and the development of new technologies. As a result, we understand much more about the molecular underpinnings of cancer biology, and this is beginning to influence clinical decision making. Further developing this base of knowledge is really the key to better implementing precision medicine.
In recent years, there has been a shift in the treatment of cancer patients from less targeted, traditional therapies toward the use of molecularly targeted therapies. This approach to treatment is known as precision medicine. It is a direct result of genomic analyses in the research laboratory being used to inform molecularly targeted drug development. As our understanding of the molecular dependencies of tumors grows, so, too, will the number of molecularly targeted drugs.
We are now witnessing great advances as genomic analyses are increasingly being applied to the clinical research setting. For example, we are using genomics to understand the molecular features of a tumor that can influence treatment decisions, tell us about the likelihood of response or resistance to certain therapies, help with diagnosis, and give clues about prognosis.
Although genomic analysis doesn’t help all patients, there is an increasing number of patients for whom it has impacted clinical decision making. For example, whole-exome sequencing of the tumor from one patient with advanced lung cancer revealed three potentially clinically relevant genetic alterations that hadn’t been detected by standard testing. As a result of our analysis, the treating physician enrolled the patient in a clinical trial that stabilized his disease for many months, which was the best response he had had to date. When that trial ended, another clinical trial was identified from which he might benefit, based on our prior genome analysis, and as a result, he continues to do well.
The use of genomics clinically has become increasingly important for understanding why there is diversity in the response of patients to anticancer therapies. We have always known that some patients respond to certain therapies and others do not, but in most cases we don’t know why these differences occur. Over the past few years, we have seen that studying “exceptional responders”—rare patients with exquisite sensitivity or unexpected long durations of response to therapies—is a good way to shed light on this issue.
We have found that in several exceptional responders, we are able to identify the mutation, or combination of mutations, that makes these patient’s tumors extraordinarily responsive to the treatments. The next step is to look for the same or similar mutations in other patients and enroll them in clinical trials to see if they, too, might respond well to the therapy. In fact, analysis of exceptional responders has seeded a number of so-called “basket” trials, in which patients are enrolled based primarily on the genetic alterations of their tumors as opposed to an anatomical basis or specific clinical features.
Genomic analysis is also key to understanding how tumors become resistant to molecularly targeted therapies. What we’ve learned is allowing us to begin to predict which patients will likely have a tumor that is resistant to a certain therapy and to identify combinations of therapies that will overcome resistance.
We are beginning to see genomic analysis move from the research setting to standard of care, but there are still challenges that must be overcome if this trend is to increase dramatically in the next few years. The key challenge is assembling enough data to support meaningful analysis. Frankly, we need data from sequencing of hundreds of thousands of tumors, submitted to large, centralized, shared databases. Moreover, the data have to be interpreted and annotated, and then communicated so that both patients and physicians can understand how to use this information in making the best treatment decisions.
The ultimate goal is for genomic analysis to be part of the routine battery of pathological and diagnostic tests run on tumor tissue from all cancer patients in order to determine the optimal care for each individual.
Nikhil Wagle, MD
Instructor in Medicine at the Dana-Farber Cancer Institute, Boston, and Associate Member of the Broad Institute, Cambridge, Massachusetts.
There's been a revolution in cancer genomics and genomics research over the past decade, thanks to the plummeting cost of sequencing and the development of new technologies. As a result, we understand much more about the molecular underpinnings of cancer biology, and this is beginning to influence clinical decision making. Further developing this base of knowledge is really the key to better implementing precision medicine.
In recent years, there has been a shift in the treatment of cancer patients from less targeted, traditional therapies toward the use of molecularly targeted therapies. This approach to treatment is known as precision medicine. It is a direct result of genomic analyses in the research laboratory being used to inform molecularly targeted drug development. As our understanding of the molecular dependencies of tumors grows, so, too, will the number of molecularly targeted drugs.
We are now witnessing great advances as genomic analyses are increasingly being applied to the clinical research setting. For example, we are using genomics to understand the molecular features of a tumor that can influence treatment decisions, tell us about the likelihood of response or resistance to certain therapies, help with diagnosis, and give clues about prognosis.
Although genomic analysis doesn’t help all patients, there is an increasing number of patients for whom it has impacted clinical decision making. For example, whole-exome sequencing of the tumor from one patient with advanced lung cancer revealed three potentially clinically relevant genetic alterations that hadn’t been detected by standard testing. As a result of our analysis, the treating physician enrolled the patient in a clinical trial that stabilized his disease for many months, which was the best response he had had to date. When that trial ended, another clinical trial was identified from which he might benefit, based on our prior genome analysis, and as a result, he continues to do well.
The use of genomics clinically has become increasingly important for understanding why there is diversity in the response of patients to anticancer therapies. We have always known that some patients respond to certain therapies and others do not, but in most cases we don’t know why these differences occur. Over the past few years, we have seen that studying “exceptional responders”—rare patients with exquisite sensitivity or unexpected long durations of response to therapies—is a good way to shed light on this issue.
We have found that in several exceptional responders, we are able to identify the mutation, or combination of mutations, that makes these patient’s tumors extraordinarily responsive to the treatments. The next step is to look for the same or similar mutations in other patients and enroll them in clinical trials to see if they, too, might respond well to the therapy. In fact, analysis of exceptional responders has seeded a number of so-called “basket” trials, in which patients are enrolled based primarily on the genetic alterations of their tumors as opposed to an anatomical basis or specific clinical features.
Genomic analysis is also key to understanding how tumors become resistant to molecularly targeted therapies. What we’ve learned is allowing us to begin to predict which patients will likely have a tumor that is resistant to a certain therapy and to identify combinations of therapies that will overcome resistance.
We are beginning to see genomic analysis move from the research setting to standard of care, but there are still challenges that must be overcome if this trend is to increase dramatically in the next few years. The key challenge is assembling enough data to support meaningful analysis. Frankly, we need data from sequencing of hundreds of thousands of tumors, submitted to large, centralized, shared databases. Moreover, the data have to be interpreted and annotated, and then communicated so that both patients and physicians can understand how to use this information in making the best treatment decisions.
The ultimate goal is for genomic analysis to be part of the routine battery of pathological and diagnostic tests run on tumor tissue from all cancer patients in order to determine the optimal care for each individual.
jueves, 23 de abril de 2015
BRCA2 ATM y Olaparib en cáncer de próstata
American Association for Cancer Research (AACR) 2015 Annual Meeting
Medscape Medical News > Conference News
Is Biomarker-Guided Treatment Coming to Prostate Cancer?
Nick Mulcahy
April 22, 2015
PHILADELPHIA — The bevy of prostate cancer treatments approved for the treatment of metastatic disease in the past few years have had, in addition to acceptable efficacy and toxicity, another commonality: none require the molecular testing that helps select patients for treatment.
This is increasingly an oddity in the era of "precision" oncology, when such testing identifies patients more likely to respond to a targeted drug.
But change could be on the way, suggests research presented here at the American Association for Cancer Research (AACR) 2015 Annual Meeting.
In a phase 1B trial from the United Kingdom, men with heavily pretreated metastatic castration-resistant prostate cancer who had certain gene mutations were much more likely to respond to treatment with the oral drug olaparib (Lynparza, AstraZeneca) than men with the disease but without the mutations, lead author Joaquin Mateo, MD, a fellow at the Institute of Cancer Research in London, said during a press briefing at the meeting.
Of the 49 patients in the TOPARP-A trial, 16 had a response to olaparib (response rate, 32.7%, 95% confidence interval [CI], 20.0 - 47.5). The response rate was the primary end point of the study. Four of the these men responded for more than 1 year, which is "quite a big achievement for a later-stage population," said Dr Mateo.
The study had a second major objective: to identify the molecular signature for sensitivity to olaparib. To that end, the investigators employed next-generation sequencing that detected mutations associated with DNA repair in tumor samples.
The genomic testing of the tumor tissues identified a set of the most prominently associated genetic mutations and deletions; 15 of the 49 men were deemed to be "biomarker positive" because of the status of these mutations and deletions. Of these 15 men, 13 had responded to olaparib (86.7%).
In other words, if a patient was a responder, chances were very high that he was biomarker positive.
The specificity of the gene panel used in the study was 94%.
"We hope that this is a step toward the molecular stratification of treatment for prostate cancer," said Dr Mateo.
However, he explained that the current trial is not a validation study of the biomarker panel. That is the next item on their research agenda for olaparib and prostate cancer, and is referred to as TOPARP-B.
Tumors lacking BRCA function are sensitive to PARP inhibition.
"For TOPARP-B, we are enrolling only patients who screen positive for the DNA-repair mutations linked to response in TOPARP-A," Dr Mateo said in a press statement.
Olaparib is a PARP inhibitor approved for use in the United States for the treatment of ovarian cancer, but only in women with BRCA mutations.
"Tumors lacking BRCA function are sensitive to PARP inhibition," said Dr Mateo.
Prostate cancers are associated with a set of genetic mutations, including BRCA2, ATM, and CHEK2, all of which are sensitive to PARP inhibitors, he explained. The biomarker suite used in this study included these mutations and a host of others.
Dr Mateo provided some context for the frequency of these mutations. Other research presented at the AACR meeting this year, he said, indicates that BRCA2 is present in about 12% of prostate cancers and ATM is present in about 7%. They are the most common of the various genetic mutations associated with prostate cancer.
New therapies for metastatic castration-resistant prostate cancer are needed, said William Nelson, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.
"Our basic hormonal therapies for prostate cancer have been around for 70 years," he pointed out. The more recent treatments, such abiraterone and enzalutamide, target the androgen receptor and have given clinicians "more mileage" in treatment. But no approach, including chemotherapy, is curative, he said, so the "next question" becomes, "What else are we going to need to target?"
This study addresses that question, suggested Dr Nelson.
Response to treatment in the study was defined as a radiologic response (n = 6), assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and biochemical response was defined as a decrease of more than 50% in prostate-specific antigen (PSA) level (n = 10).
For the men in this study, average age was 67.5 years, performance status ranged from 0 to 2 (80% were either 0 or 1), and the average duration of castration-resistant prostate cancer was 2.2 years.
Mean baseline PSA was very high (349.5 µg/L). All of the men had received previous chemotherapy, and 96% had received abiraterone. In addition, about one-quarter had received enzalutamide and about one-quarter had been treated with radiotherapy.
The study was supported by funds from the Cancer Research UK Clinical Trials Awards and Advisory Committee, SU2C, PCF, the Experimental Cancer Medicine Center, and the UK National Institute for Health Research Biomedical Research Center. Dr Mateo has disclosed no relevant financial relationships. Senior author Johann de Bono, MD, from The Institute of Cancer Research and The Royal Marsden in Sutton, United Kingdom, reports financial ties to AstraZeneca.
American Association for Cancer Research (AACR) 2015 Annual Meeting: Abstract 8311. Presented April 21, 2015.
Medscape Medical News > Conference News
Is Biomarker-Guided Treatment Coming to Prostate Cancer?
Nick Mulcahy
April 22, 2015
PHILADELPHIA — The bevy of prostate cancer treatments approved for the treatment of metastatic disease in the past few years have had, in addition to acceptable efficacy and toxicity, another commonality: none require the molecular testing that helps select patients for treatment.
This is increasingly an oddity in the era of "precision" oncology, when such testing identifies patients more likely to respond to a targeted drug.
But change could be on the way, suggests research presented here at the American Association for Cancer Research (AACR) 2015 Annual Meeting.
In a phase 1B trial from the United Kingdom, men with heavily pretreated metastatic castration-resistant prostate cancer who had certain gene mutations were much more likely to respond to treatment with the oral drug olaparib (Lynparza, AstraZeneca) than men with the disease but without the mutations, lead author Joaquin Mateo, MD, a fellow at the Institute of Cancer Research in London, said during a press briefing at the meeting.
Of the 49 patients in the TOPARP-A trial, 16 had a response to olaparib (response rate, 32.7%, 95% confidence interval [CI], 20.0 - 47.5). The response rate was the primary end point of the study. Four of the these men responded for more than 1 year, which is "quite a big achievement for a later-stage population," said Dr Mateo.
The study had a second major objective: to identify the molecular signature for sensitivity to olaparib. To that end, the investigators employed next-generation sequencing that detected mutations associated with DNA repair in tumor samples.
The genomic testing of the tumor tissues identified a set of the most prominently associated genetic mutations and deletions; 15 of the 49 men were deemed to be "biomarker positive" because of the status of these mutations and deletions. Of these 15 men, 13 had responded to olaparib (86.7%).
In other words, if a patient was a responder, chances were very high that he was biomarker positive.
The specificity of the gene panel used in the study was 94%.
"We hope that this is a step toward the molecular stratification of treatment for prostate cancer," said Dr Mateo.
However, he explained that the current trial is not a validation study of the biomarker panel. That is the next item on their research agenda for olaparib and prostate cancer, and is referred to as TOPARP-B.
Tumors lacking BRCA function are sensitive to PARP inhibition.
"For TOPARP-B, we are enrolling only patients who screen positive for the DNA-repair mutations linked to response in TOPARP-A," Dr Mateo said in a press statement.
Olaparib is a PARP inhibitor approved for use in the United States for the treatment of ovarian cancer, but only in women with BRCA mutations.
"Tumors lacking BRCA function are sensitive to PARP inhibition," said Dr Mateo.
Prostate cancers are associated with a set of genetic mutations, including BRCA2, ATM, and CHEK2, all of which are sensitive to PARP inhibitors, he explained. The biomarker suite used in this study included these mutations and a host of others.
Dr Mateo provided some context for the frequency of these mutations. Other research presented at the AACR meeting this year, he said, indicates that BRCA2 is present in about 12% of prostate cancers and ATM is present in about 7%. They are the most common of the various genetic mutations associated with prostate cancer.
New therapies for metastatic castration-resistant prostate cancer are needed, said William Nelson, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore.
"Our basic hormonal therapies for prostate cancer have been around for 70 years," he pointed out. The more recent treatments, such abiraterone and enzalutamide, target the androgen receptor and have given clinicians "more mileage" in treatment. But no approach, including chemotherapy, is curative, he said, so the "next question" becomes, "What else are we going to need to target?"
This study addresses that question, suggested Dr Nelson.
Response to treatment in the study was defined as a radiologic response (n = 6), assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, and biochemical response was defined as a decrease of more than 50% in prostate-specific antigen (PSA) level (n = 10).
For the men in this study, average age was 67.5 years, performance status ranged from 0 to 2 (80% were either 0 or 1), and the average duration of castration-resistant prostate cancer was 2.2 years.
Mean baseline PSA was very high (349.5 µg/L). All of the men had received previous chemotherapy, and 96% had received abiraterone. In addition, about one-quarter had received enzalutamide and about one-quarter had been treated with radiotherapy.
The study was supported by funds from the Cancer Research UK Clinical Trials Awards and Advisory Committee, SU2C, PCF, the Experimental Cancer Medicine Center, and the UK National Institute for Health Research Biomedical Research Center. Dr Mateo has disclosed no relevant financial relationships. Senior author Johann de Bono, MD, from The Institute of Cancer Research and The Royal Marsden in Sutton, United Kingdom, reports financial ties to AstraZeneca.
American Association for Cancer Research (AACR) 2015 Annual Meeting: Abstract 8311. Presented April 21, 2015.
miércoles, 22 de abril de 2015
Inhibidores PLK1, Aurora Kinasa A, Aurora Kinasa B, nuevos retos nuevas esperanzas
Co-inhibition of polo-like kinase 1 and aurora kinases promotes mitotic catastrophe
Jingjing Li, _ Myung Jin Hong, Jeremy P.H. Chow, Wing Yu Man, Joyce P.Y. Mak, Hoi Tang Ma, Randy Y.C. Poon
Jingjing Li, Myung Jin Hong, Jeremy P.H. Chow, Wing Yu Man, Joyce P.Y. Mak, Hoi Tang Ma, Randy Y.C. Poon
Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
Correspondence to: Randy Y.C. Poon, e-mail: rycpoon@ust.hk Keywords: anticancer drugs, antimitotic drugs, kinases, mitosis, mitotic slippage
Received: November 04, 2014 Accepted: February 08, 2015 Published: March 20, 2015
ABSTRACT
Mitosis is choreographed by a number of protein kinases including polo-like kinases and Aurora kinases. As these kinases are frequently dysregulated in cancers, small-molecule inhibitors have been developed for targeted anticancer therapies. Given that PLK1 and Aurora kinases possess both unique functions as well as co-regulate multiple mitotic events, whether pharmacological inhibition of these kinases together can enhance mitotic catastrophe remains an outstanding issue to be determined. Using concentrations of inhibitors that did not induce severe mitotic defects on their own, we found that both the metaphase arrest and mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108 and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly invasive cancer with poor prognosis, in comparison to normal nasopharyngeal epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536 as a single agent and co-inhibition with Aurora kinases than normal cells. These observations underscore the mechanism and potential benefits of targeting PLK1 and Aurora kinases to induce mitotic catastrophe in cancer cells.
INTRODUCTION
Accurate cell division relies on the actions of a well-balanced network of protein kinases and phosphatases [1]. Polo-like kinases and Aurora kinases are two of the most studied families of mitotic kinases. These kinases performs multiple functions in mitosis, including centrosome maturation, kinetochore-spindle attachment, chromosome segregation, and cytokinesis.
One of the critical functions of polo-like kinase 1(PLK1) in mitosis is for kick-starting the autocatalytic loop that controls the activity of cyclin B1–CDK1 [2]. Phosphorylation by PLK1 promotes the activation of CDC25 [3–5] and inactivation of WEE1 [6,7]. In addition to regulating cyclin B1–CDK1 activity through the CDC25/WEE1 axis, PLK1 also controls the localization of cyclin B1 by phosphorylating its nuclear export sequence. This inhibits the binding of the export receptor CRM1, thereby triggering nuclear accumulation and activation of cyclin B1 during prophase [8].
Similarly to many protein kinases, PLK1 activation requires phosphorylation of a residue on the T-loop (Thr210). PLK1Thr210 is phosphorylated by Aurora A (also called AURKA), an event that is assisted by Bora [9]. PLK1 in turn promotes the recruitment of AURKA to the centrosomes in late G2 [10]. PLK1 also phosphorylates Bora, generating a phosphodegron motif that is recognized by the ubiquitin ligase SCFβ–TrCP, thereby triggering Bora destruction [11]. Degradation of Bora is believed to be important for redistributing AURKA from a cytoplasmic Bora-containing complex to a TPX2-containing complex at the mitotic spindle. The TPX2–AURKA complex then promotes centrosome maturation and bipolar spindle formation in a Ran- GTP-dependent manner [12].
Although highly related to AURKA, Aurora B (also called AURKB) is a component of the chromosomal passenger complex (CPC), which is comprised of AURKB, INCENP, borealin, and survivin [13]. CPC localizes to chromosomes and kinetochores in early mitosis and functions in chromosome–microtubule interactions, sister chromatid cohesion, and the spindle-assembly checkpoint. In early mitosis, PLK1Thr210 is phosphorylated by AURKB at centromeres and kinetochores [14]. In anaphase, the CPC is relocated to the mid-zone to promote cytokinesis.
The activity of AURKA increases from late G2 phase onwards and peaks during prometaphase. On the other hand, the activity of AURKB peaks from metaphase to the end of mitosis. Activation of AURKA requires binding to specific cofactors including Ajuba, Bora, and TPX2, leading to the autophosphorylation of a residue in the T-loop (Thr288) [15]. Similarly, AURKB is activated by autophosphorylation of the T-loop (Thr232) after binding to members of the CPC [16]. At the end of mitosis, both AURKA and AURKB are degraded by APC/C-mediated ubiquitination.
Although PLK1, AURKA, and AURKB have their unique functions during mitosis, they also co-regulate multiple processes, including entry into mitosis, mitotic spindle formation, sister chromatid resolution, chromosome–spindle connections, and cytokinesis. Mechanistically, these kinases often phosphorylate different components involve in the same mitotic process [17].
As Aurora kinases are upregulated in several human cancers and correlated with poor prognosis, they are believed to be important anticancer drug targets [18]. More than 20 small-molecule Aurora kinase inhibitors have been developed and are at various stages of clinical trials [19]. While the early generations of Aurora kinase inhibitors inactivate both AURKA and AURKB indiscriminately, later generations of inhibitors are able to target AURKA or AURKB specifically. Similarly, scores of anticancer drug candidates targeting PLK1 have been developed [20].
Inhibition of PLK1 or the two Aurora kinases triggers a process generally termed mitotic catastrophe. More recent attempts to standardize the term mitotic catastrophe defined it to be associated with aberrant mitotic activity that ultimately triggers cell death or irreversible cell cycle arrest [21]. In this definition, cell death can occur either during or after the defective mitosis such as mitotic slippage.
Given the close relationship between PLK1 and the Aurora kinases, a salient question is the biological consequences when these kinases are targeted together. Will inhibitors of PLK1 and Aurora kinases synergistically enhance a particular mitotic defect? Or will they antagonize each other, causing different defects as if they act independently? Here we address these questions directly at single cells level using live-cell imaging, in particular comparing normal and cancer cells from nasopharyngeal carcinoma.
Jingjing Li, _ Myung Jin Hong, Jeremy P.H. Chow, Wing Yu Man, Joyce P.Y. Mak, Hoi Tang Ma, Randy Y.C. Poon
Jingjing Li, Myung Jin Hong, Jeremy P.H. Chow, Wing Yu Man, Joyce P.Y. Mak, Hoi Tang Ma, Randy Y.C. Poon
Division of Life Science, Center for Cancer Research, and State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong
Correspondence to: Randy Y.C. Poon, e-mail: rycpoon@ust.hk Keywords: anticancer drugs, antimitotic drugs, kinases, mitosis, mitotic slippage
Received: November 04, 2014 Accepted: February 08, 2015 Published: March 20, 2015
ABSTRACT
Mitosis is choreographed by a number of protein kinases including polo-like kinases and Aurora kinases. As these kinases are frequently dysregulated in cancers, small-molecule inhibitors have been developed for targeted anticancer therapies. Given that PLK1 and Aurora kinases possess both unique functions as well as co-regulate multiple mitotic events, whether pharmacological inhibition of these kinases together can enhance mitotic catastrophe remains an outstanding issue to be determined. Using concentrations of inhibitors that did not induce severe mitotic defects on their own, we found that both the metaphase arrest and mitotic slippage induced by inhibitors targeting Aurora A and Aurora B (MK-5108 and Barasertib respectively) were enhanced by a PLK1 inhibitor (BI 2536). We found that PLK1 is overexpressed in cells from nasopharyngeal carcinoma, a highly invasive cancer with poor prognosis, in comparison to normal nasopharyngeal epithelial cells. Nasopharyngeal carcinoma cells were more sensitive to BI 2536 as a single agent and co-inhibition with Aurora kinases than normal cells. These observations underscore the mechanism and potential benefits of targeting PLK1 and Aurora kinases to induce mitotic catastrophe in cancer cells.
INTRODUCTION
Accurate cell division relies on the actions of a well-balanced network of protein kinases and phosphatases [1]. Polo-like kinases and Aurora kinases are two of the most studied families of mitotic kinases. These kinases performs multiple functions in mitosis, including centrosome maturation, kinetochore-spindle attachment, chromosome segregation, and cytokinesis.
One of the critical functions of polo-like kinase 1(PLK1) in mitosis is for kick-starting the autocatalytic loop that controls the activity of cyclin B1–CDK1 [2]. Phosphorylation by PLK1 promotes the activation of CDC25 [3–5] and inactivation of WEE1 [6,7]. In addition to regulating cyclin B1–CDK1 activity through the CDC25/WEE1 axis, PLK1 also controls the localization of cyclin B1 by phosphorylating its nuclear export sequence. This inhibits the binding of the export receptor CRM1, thereby triggering nuclear accumulation and activation of cyclin B1 during prophase [8].
Similarly to many protein kinases, PLK1 activation requires phosphorylation of a residue on the T-loop (Thr210). PLK1Thr210 is phosphorylated by Aurora A (also called AURKA), an event that is assisted by Bora [9]. PLK1 in turn promotes the recruitment of AURKA to the centrosomes in late G2 [10]. PLK1 also phosphorylates Bora, generating a phosphodegron motif that is recognized by the ubiquitin ligase SCFβ–TrCP, thereby triggering Bora destruction [11]. Degradation of Bora is believed to be important for redistributing AURKA from a cytoplasmic Bora-containing complex to a TPX2-containing complex at the mitotic spindle. The TPX2–AURKA complex then promotes centrosome maturation and bipolar spindle formation in a Ran- GTP-dependent manner [12].
Although highly related to AURKA, Aurora B (also called AURKB) is a component of the chromosomal passenger complex (CPC), which is comprised of AURKB, INCENP, borealin, and survivin [13]. CPC localizes to chromosomes and kinetochores in early mitosis and functions in chromosome–microtubule interactions, sister chromatid cohesion, and the spindle-assembly checkpoint. In early mitosis, PLK1Thr210 is phosphorylated by AURKB at centromeres and kinetochores [14]. In anaphase, the CPC is relocated to the mid-zone to promote cytokinesis.
The activity of AURKA increases from late G2 phase onwards and peaks during prometaphase. On the other hand, the activity of AURKB peaks from metaphase to the end of mitosis. Activation of AURKA requires binding to specific cofactors including Ajuba, Bora, and TPX2, leading to the autophosphorylation of a residue in the T-loop (Thr288) [15]. Similarly, AURKB is activated by autophosphorylation of the T-loop (Thr232) after binding to members of the CPC [16]. At the end of mitosis, both AURKA and AURKB are degraded by APC/C-mediated ubiquitination.
Although PLK1, AURKA, and AURKB have their unique functions during mitosis, they also co-regulate multiple processes, including entry into mitosis, mitotic spindle formation, sister chromatid resolution, chromosome–spindle connections, and cytokinesis. Mechanistically, these kinases often phosphorylate different components involve in the same mitotic process [17].
As Aurora kinases are upregulated in several human cancers and correlated with poor prognosis, they are believed to be important anticancer drug targets [18]. More than 20 small-molecule Aurora kinase inhibitors have been developed and are at various stages of clinical trials [19]. While the early generations of Aurora kinase inhibitors inactivate both AURKA and AURKB indiscriminately, later generations of inhibitors are able to target AURKA or AURKB specifically. Similarly, scores of anticancer drug candidates targeting PLK1 have been developed [20].
Inhibition of PLK1 or the two Aurora kinases triggers a process generally termed mitotic catastrophe. More recent attempts to standardize the term mitotic catastrophe defined it to be associated with aberrant mitotic activity that ultimately triggers cell death or irreversible cell cycle arrest [21]. In this definition, cell death can occur either during or after the defective mitosis such as mitotic slippage.
Given the close relationship between PLK1 and the Aurora kinases, a salient question is the biological consequences when these kinases are targeted together. Will inhibitors of PLK1 and Aurora kinases synergistically enhance a particular mitotic defect? Or will they antagonize each other, causing different defects as if they act independently? Here we address these questions directly at single cells level using live-cell imaging, in particular comparing normal and cancer cells from nasopharyngeal carcinoma.
Inhibidores PLK1
See comment in PubMed Commons below
Leukemia. 2015 Jan;29(1):11-9. doi: 10.1038/leu.2014.222. Epub 2014 Jul 16.
Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy.
Gjertsen BT1, Schöffski P2.
Author information11] Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.2Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
Abstract
Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on volasertib (BI 6727; an investigational agent), a potent and selective Plk inhibitor. Volasertib has shown promising activity in various cancer cell lines and xenograft models of human cancer. Trials performed to date suggest that volasertib has clinical efficacy in a range of malignancies, with the most promising results seen in patients with acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that volasertib combined with low-dose cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile, volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biologic rationale for Plk1 inhibitors in cancer, the clinical development of volasertib to date in solid tumors and AML, and the future identification of biomarkers that might predict response to volasertib and help determine the role of this agent in the clinic.
PMID:25027517[PubMed - indexed for MEDLINE] PMCID:PMC4335352Free PMC Article
Leukemia. 2015 Jan;29(1):11-9. doi: 10.1038/leu.2014.222. Epub 2014 Jul 16.
Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy.
Gjertsen BT1, Schöffski P2.
Author information11] Centre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway [2] Department of Internal Medicine, Haematology Section, Haukeland University Hospital, Bergen, Norway.2Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
Abstract
Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on volasertib (BI 6727; an investigational agent), a potent and selective Plk inhibitor. Volasertib has shown promising activity in various cancer cell lines and xenograft models of human cancer. Trials performed to date suggest that volasertib has clinical efficacy in a range of malignancies, with the most promising results seen in patients with acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that volasertib combined with low-dose cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile, volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biologic rationale for Plk1 inhibitors in cancer, the clinical development of volasertib to date in solid tumors and AML, and the future identification of biomarkers that might predict response to volasertib and help determine the role of this agent in the clinic.
PMID:25027517[PubMed - indexed for MEDLINE] PMCID:PMC4335352Free PMC Article
martes, 21 de abril de 2015
Inhibidor Kinasa "polo like", parte de una nueva familia de fármacos para el tratamiento del cáncer
Targeting Mitosis: First Polo-Like Kinase Inhibitor Moves Closer to FDA Approval
Jane de Lartigue, PhD
Published Online: Thursday, September 25, 2014
Cancer Cell
The concept of targeting mitotic cell division to halt the progression of rapidly dividing cancer cells has long been a staple of oncology therapy, yet chemotherapy agents that are the prime examples of this approach are nonselective in their action and can kill normal and malignant cells alike. Now, novel targeted approaches focusing on the inhibition of mitotic kinases are showing significant promise.
Among them are agents targeting polo-like kinase 1 (Plk1), which plays an important role throughout mitosis. Despite some clinical disappointment, a greater understanding of the intricate molecular mechanisms underlying the progression of the cell cycle and the respective roles of the PLK kinase family has offered renewed hope.
The lead agent in this category is volasertib, which has achieved breakthrough therapy and orphan drug designations from the FDA, and expectations are high for late-stage clinical testing that may result in the first approved agent in this class.
Rationale for Focusing on PLK
One of the hallmarks of cancer is unchecked cell division and, as such, targeting mitosis in these rapidly dividing cells has become a validated therapeutic approach. In recent years, researchers have identified various “checkpoints” that ensure cell division occurs at the appropriate time—and that may become dysregulated in human cancers.
Many of these checkpoints are controlled by protein kinases, among them the PLKs, a family of serine/threonine kinases. There are five members of the PLK family: Plks 1 through 5. Although they have different functions and tissue locations, most share a similar structure. At one end of the protein is the serine/threonine kinase domain (except for Plk5 which seems to lack a functional kinase domain) that is responsible for catalytic activity, while at the other end is a polo-box domain (PBD). The PBD is a regulatory domain that controls kinase activity; it prevents the kinase domain from binding to its target proteins until it receives the appropriate activation signal.
Plk1 is the most well characterized member of the family. The Plk1 protein is only expressed in dividing cells and its levels fluctuate during the course of the cell cycle. Its activity peaks during mitosis (M) phase, where it is involved in almost every step of mitotic cell division via the phosphorylation of a wide variety of downstream targets, including cyclin B1 and CDC25, which trigger entry into mitosis. Plk1 also regulates other mitotic events such as spindle formation and chromosome segregation.
Mitotic Roles of Plk1
Polo-like kinase 1 (Plk1) is activated throughout the process of mitotic regulation and cell division, with its peak expression during the G2/M phase of the cycle, as illustrated above.
G1 indicates growth 1 phase of the cell cycle; G2, growth 2; M, mitosis.
Donaldson MM, et al. The mitotic roles of polo-like kinase. J Cell Sci. 2001;114(13):2357-2358. jcs.biologists.org. Adapted with permission.
Plk1 and other mitotic kinases act as cell cycle checkpoints, so that entry into mitosis and subsequent cell division and proliferation is prevented in the absence of appropriate signals. High levels of Plk1 essentially permit the cancer cell to pass through these checkpoints unimpeded, contributing to the hallmark unchecked cell division and proliferation observed in tumors. Although evidence that Plk1 as an oncogene is lacking, it is frequently overexpressed in many different cancer types, including non–small cell lung cancer (NSCLC), melanoma, colorectal carcinoma, and prostate cancer, and high levels of Plk1 expression often correlate with poor prognosis.
The cellular roles of the other PLKs are less clear. However, several studies have suggested that Plk2 and Plk3 may in fact have opposing functions to the proliferative role of Plk1 and act as tumor suppressors or at the very least have functions that are unrelated to cancer cell proliferation. The PLK2 gene has been shown to be frequently methylated and silenced in B cell malignancies, while reduced expression of Plk3 proteins has been observed in several cancer types.
Since Plk1 is highly expressed in cancer cells, but not in nondividing healthy cells, it represents an attractive means to target mitosis in a more specific manner than chemotherapeutics. There has been significant research and development in this area and a number of Plk1-targeting agents have been investigated.
Volasertib Leads the Class
A common method of inhibiting protein kinases is to develop compounds that target the adenosine triphosphate (ATP) binding site. As the name implies, these ATP-competitive inhibitors compete with ATP for binding to the kinase and thus prevent its activation. The first Plk1 inhibitors were designed, as such, to be ATP-competitive inhibitors.
Jane de Lartigue, PhD
Published Online: Thursday, September 25, 2014
Cancer Cell
The concept of targeting mitotic cell division to halt the progression of rapidly dividing cancer cells has long been a staple of oncology therapy, yet chemotherapy agents that are the prime examples of this approach are nonselective in their action and can kill normal and malignant cells alike. Now, novel targeted approaches focusing on the inhibition of mitotic kinases are showing significant promise.
Among them are agents targeting polo-like kinase 1 (Plk1), which plays an important role throughout mitosis. Despite some clinical disappointment, a greater understanding of the intricate molecular mechanisms underlying the progression of the cell cycle and the respective roles of the PLK kinase family has offered renewed hope.
The lead agent in this category is volasertib, which has achieved breakthrough therapy and orphan drug designations from the FDA, and expectations are high for late-stage clinical testing that may result in the first approved agent in this class.
One of the hallmarks of cancer is unchecked cell division and, as such, targeting mitosis in these rapidly dividing cells has become a validated therapeutic approach. In recent years, researchers have identified various “checkpoints” that ensure cell division occurs at the appropriate time—and that may become dysregulated in human cancers.
Many of these checkpoints are controlled by protein kinases, among them the PLKs, a family of serine/threonine kinases. There are five members of the PLK family: Plks 1 through 5. Although they have different functions and tissue locations, most share a similar structure. At one end of the protein is the serine/threonine kinase domain (except for Plk5 which seems to lack a functional kinase domain) that is responsible for catalytic activity, while at the other end is a polo-box domain (PBD). The PBD is a regulatory domain that controls kinase activity; it prevents the kinase domain from binding to its target proteins until it receives the appropriate activation signal.
Plk1 is the most well characterized member of the family. The Plk1 protein is only expressed in dividing cells and its levels fluctuate during the course of the cell cycle. Its activity peaks during mitosis (M) phase, where it is involved in almost every step of mitotic cell division via the phosphorylation of a wide variety of downstream targets, including cyclin B1 and CDC25, which trigger entry into mitosis. Plk1 also regulates other mitotic events such as spindle formation and chromosome segregation.
Mitotic Roles of Plk1
Polo-like kinase 1 (Plk1) is activated throughout the process of mitotic regulation and cell division, with its peak expression during the G2/M phase of the cycle, as illustrated above.
G1 indicates growth 1 phase of the cell cycle; G2, growth 2; M, mitosis.
Donaldson MM, et al. The mitotic roles of polo-like kinase. J Cell Sci. 2001;114(13):2357-2358. jcs.biologists.org. Adapted with permission.
Plk1 and other mitotic kinases act as cell cycle checkpoints, so that entry into mitosis and subsequent cell division and proliferation is prevented in the absence of appropriate signals. High levels of Plk1 essentially permit the cancer cell to pass through these checkpoints unimpeded, contributing to the hallmark unchecked cell division and proliferation observed in tumors. Although evidence that Plk1 as an oncogene is lacking, it is frequently overexpressed in many different cancer types, including non–small cell lung cancer (NSCLC), melanoma, colorectal carcinoma, and prostate cancer, and high levels of Plk1 expression often correlate with poor prognosis.
The cellular roles of the other PLKs are less clear. However, several studies have suggested that Plk2 and Plk3 may in fact have opposing functions to the proliferative role of Plk1 and act as tumor suppressors or at the very least have functions that are unrelated to cancer cell proliferation. The PLK2 gene has been shown to be frequently methylated and silenced in B cell malignancies, while reduced expression of Plk3 proteins has been observed in several cancer types.
Since Plk1 is highly expressed in cancer cells, but not in nondividing healthy cells, it represents an attractive means to target mitosis in a more specific manner than chemotherapeutics. There has been significant research and development in this area and a number of Plk1-targeting agents have been investigated.
Volasertib Leads the Class
A common method of inhibiting protein kinases is to develop compounds that target the adenosine triphosphate (ATP) binding site. As the name implies, these ATP-competitive inhibitors compete with ATP for binding to the kinase and thus prevent its activation. The first Plk1 inhibitors were designed, as such, to be ATP-competitive inhibitors.
Desnutrición en el paciente oncológico. Reportaje SEOM
Contigo oncología para el paciente y su entorno
Las repercusiones de la alimentación sobre la salud se conocen
desde la época de Hipócrates, el primer médico que describe y pone nombre
al cáncer, que afirmaba cuatro siglos antes de Cristo que “el vigor del hambre
puede influir violentamente en la constitución del hombre, debilitándolo, haciéndolo
enfermar e, incluso, sucumbir”.
Antes de adentrarnos en materia, cabe matizar que un paciente está malnutrido cuando presenta un cuadro clínico caracterizado por un desequilibrio entre la ingesta de nutrientes y las necesidades nutricionales básicas.
Si este desequilibrio es negativo, se habla de desnutrición. En el caso del enfermo oncológico, aparecen la malnutrición y la desnutrición.
La malnutrición asociada al cáncer es un factor de mal pronóstico, independientemente del tumor, tanto para la supervivencia como para la respuesta al tratamiento.
Magdalena García Huerta, del Servicio de Endocrinología y Nutrición
del Hospital Universitario La Paz, de Madrid, nos explica que “una mala
alimentación en el enfermo neoplásico produce disfunción inmunológica y deficiencias
en zinc, hierro, vitaminas A, B6, B12, D y E y ácido fólico, así como alteraciones
lipídicas (exceso de colesterol y ácidos grasos libres y déficit de ácidos
grasos esenciales)”. El porcentaje de enfermos oncológicos
que presenta malnutrición oscila entre el 15 y el 40 por ciento en el
momento de realizar el diagnóstico, aunque estas cifras aumentan hasta un 80
por ciento en los casos de enfermedad avanzada.
El enfermo neoplásico presenta malnutrición como consecuencia de la biología tumoral maligna y del tratamiento oncológico.
El cáncer produce disminución de la ingesta de forma directa, interfiriendo de forma mecánica con el tránsito normal del tubo digestivo, o de forma indirecta, a través de la secreción de sustancias que actúan sobre receptores periféricos o sobre el hipotálamo.
Los tumores localizados en el tubo digestivo (faringe, esófago, estómago y
páncreas) provocan obstrucción de forma directa o sensación de saciedad
precoz por limitación de la capacidad gástrica. Un efecto similar se observa en
tumores que derivan de otros órganos, pero que producen una comprensión
extrínseca del estómago. Es típico el desplazamiento gástrico que ocasionan
algunos de los síntomas de las metástasis hepáticas, así como la obstrucción
intestinal asociada a los implantes peritoneales de los tumores ováricos, pancreáticos
o gástricos.
Los tumores de cabeza y cuello, esófago, estómago, páncreas, colon y
recto son los que causan una malnutrición más severa, mientras que el cáncer
de mama, próstata, pulmón, algunos linfomas y la leucemia casi no alteran el
estado nutricional de los enfermos.
En este sentido, García Huerta nos comenta que “en casos de cánceres gástricos y de páncreas, la pérdida de peso es del 10 por ciento en un tercio de los pacientes, teniendo una incidencia de caquexia [léase más adelante] de entre el 83 y el 87 por ciento”.
En un estudio retrospectivo del Eastern Cooperative Oncology Group
(ECOG), realizado en 3.047 pacientes que iban a iniciar sesiones de quimioterapia,
se observó que el 50 por ciento ya habían perdido peso antes del tratamiento,
y que un 15 por ciento habían perdido más del 10 por ciento de su
peso habitual.
La malnutrición conlleva una mayor morbilidad en los enfermos neoplásicos, por lo que es prioritario realizar una adecuada valoración de su estado nutricional, tanto en el diagnóstico de la enfermedad como de forma seriada, en distintos momentos de la evolución del cáncer.
La especialista del Servicio de Endocrinología y Nutrición del Hospital La
Paz nos explica los diferentes métodos para identificar a pacientes con malnutrición
o con un riesgo significativo de complicaciones: “Estos procedimientos
pueden basarse en parámetros antropométricos (peso, talla, índice de masa
corporal -IMC-, pliegues cutáneos y circunferencia muscular del brazo), en la
medición de proteínas plasmáticas (albúmina, transferrina) y en la Valoración
Global Subjetiva (VGS)”.
La Valoración Global Subjetiva Generada por el Paciente (VGS-GP) es el test de valoración del estado nutricional más utilizado en la actualidad, al contar con una buena relación costeefectividad al poder ser aplicable por cualquier miembro del personal sanitario con un nivel mínimo de adiestramiento y, sobre todo, al ayudar en la toma de decisión sobre el tratamiento nutricional más adecuado.
Se trata de un método diseñado por Detsky y col. en 1987 en el Hospital General de
Toronto, basado en la historia clínica del enfermo y en su exploración física.
“Este método es sensible, específico y presenta poca variabilidad entre
observadores, clasificando a los pacientes en tres grupos: categoría A
(adecuado estado nutricional), categoría B (sospecha de malnutrición o malnutrición
moderada) y categoría C (malnutrición severa)”, destaca Magdalena
García Huerta.
La desnutrición también disminuye considerablemente la calidad de vida
de los enfermos neoplásicos, sobre todo por su influencia sobre la fuerza
muscular y la sensación de debilidad y de cansancio o astenia, así como por el
impacto psicológico, que puede inducir síntomas depresivos. Todas estas
situaciones complican el cuadro y disminuyen la autonomía del enfermo, lo
que alarga su estancia en el hospital.
El síndrome anorexia-caquexia es una manifestación multiorgánica que
provoca numerosas complicaciones fisiológicas y funcionales. El término
caquexia deriva del griego “kakos” y “hexis”, que significa “mal estado o
condición”. Los términos caquexia y malnutrición siempre van asociados, ya
que siempre que hay caquexia aparece la malnutrición.
La caquexia se caracteriza por una pérdida progresiva de peso de forma
involuntaria, acompañada de anorexia (disminución en la ingesta), astenia
(debilidad y letargo), atrofia muscular y alteraciones inmunes y de la capacidad
de atención y concentración. A menudo aparecen náuseas, alteraciones del
gusto y olfato, anemia, sensación de saciedad precoz y estreñimiento.
La caquexia tiene sus orígenes en dos aspectos fundamentales: el aumento
de demanda calórica por la presencia del tumor y la malnutrición debida a la
anorexia. Los factores desencadenantes del síndrome pueden ser de origen
tumoral o humoral (citoquinas producidas por el huésped en respuesta al
tumor -o por el propio tumor- y alteraciones hormonales).
El síndrome de la caquexia cancerosa alcanza aproximadamente al 70 por
ciento de los pacientes en un estadio avanzado de la enfermedad y es directamente
responsable de la muerte de, al menos, el 22 por ciento de los pacientes
oncológicos. La caquexia afecta a numerosos órganos tejidos del cuerpo como el músculoesquelético (representa casi el 40 por ciento de nuestro peso), lo que provoca pérdida de fuerza y disminución de resistencia al esfuerzo; la piel (adelgazamiento y pérdida de elasticidad, facilidad para contraer úlceras decúbito, cabello ralo y seco o uñas quebradizas); corazón (disminuye la masa cardiaca y el índice cardiaco) o el hígado.
También afecta al riñón, al aparato respiratorio y gastrointestinal y a los sistemas nervioso e inmunitario.
Actualmente, existen multitud de armas terapéuticas para combatir el síndrome
anorexia-caquexia. García Huerta nos explica que “los medicamentos más recomendables
son los ácidos grasos omega-3, que son moléculas fundamentalmente
anticatabólicas que impiden la degradación de las proteínas musculares; la leucina,
un aminoácido esencial que estimula la síntesis proteica a nivel muscular e inhibe
el sistema proteolítico (degradación muscular), y la metionina, otro aminoácido
esencial que consigue potenciar el efecto de la leucina”.
Como fármacos estimulantes del apetito se utilizan los corticosteroides,
los cannabinoides (la marihuana y sus derivados estimulan el apetito, aunque
no hay estudios que permitan recomendar su utilización) y los progestágenos.
Como fármacos procinéticos (profilaxis de náuseas y vómitos) se utiliza fundamentalmente la metoclopramida, y como fármacos inhibidores del catabolismo
están el sulfato de hidracina, la pentoxifilina y la talidomida, entre otros.
También se estudian nuevas alternativas terapéuticas como la melatonina,
una de las sustancias que cuenta con mayor futuro potencial en el tratamiento
de la caquexia tumoral y cuyo mecanismo de acción se desarrolla a través de
la inhibición de las citoquinas. La dieta oral en algunos pacientes
con cáncer puede plantear serias dificultades, por lo que se recomienda la nutrición
artificial, bien por vía enteral o parenteral.
La nutrición enteral puede definirse como el aporte de nutrientes por vía
digestiva, ya sea a través de sondas nasoentéricas, catéteres de ostomía (abertura
en el abdomen) o vía oral a intervalos regulares, siempre que la cantidad que
debe administrarse supere las 1.000 kcal o 40 gramos de proteínas al día. Se
trata de una técnica de bajo coste, más fisiológica y más fácil de mantener.
Para entender bien todos estos conceptos, cabe destacar que existen dos
vías de acceso al tracto gastrointestinal: nasal (vía naso-gástrica, naso-yeyunal y
naso-duodenal) y ostomías (gastrostomía y yeyunostomía).
La vía nasogástrica es el método más simple y consiste en la administración
de los nutrientes a través de sondas fabricadas en silicona o poliuretano.
Esta alternativa es recomendada para nutriciones de no más de seis semanas y
su principal inconveniente es que resulta molesta para el paciente. Por su parte,
la gastrostomía supone el establecimiento de una fístula gastro-cutánea dirigida
sobre tubo y se recomienda para pacientes que requieren nutrición enteral
prolongada.
La nutrición parenteral consiste en administrar nutrientes al organismo por
vía extradigestiva, es decir, a través del torrente sanguíneo, sin el proceso digestivo y filtro hepático natural. Además de que supone una elevada carga asistencial y un coste económico considerable, este tipo de nutrición conlleva complicaciones por la elevada incidencia de infecciones y los problemas atribuibles al exceso o déficit de nutrientes. De hecho, e de los 40 estudios realizados hasta la un tumor fecha, se concluye que el beneficio de esta técnica en pacientes oncológicos
es muy dudoso. La nutrición parenteral está indicada en pacientes cuyo tracto gastrointestinal no es utilizable para la administración, digestión o absorción de nutrientes durante un periodo superior a 5-7 días, o cuando el tubo digestivo es utilizable pero se desea mantener en reposo por razones terapéuticas.
Como alternativa a la alimentación tradicional, surge la Alimentación Básica
Adaptada (ABA), que ofrece una serie de productos que se adaptan a las necesidades
del paciente en nutrientes y textura, es de fácil preparación, mantiene el
aspecto de “plato hecho en casa” y tiene un sabor identificable con la alimentación
casera. Actualmente, existen preparados en forma de purés, listos para su consumo,
o en forma de puré instantáneo, liofilizado, presentado en polvo para ser
reconstituido con caldo, agua, leche y un poco de aceite. También existen preparados
a base de cereales y frutas, con textura suave y homogénea, así como postres
de frutas listas para consumir en forma de compota instantánea para mezclar
con agua o zumo.
El oncólogo y escritor Francesc Casas puso en marcha en diciembre del
año pasado un estudio de un año de duración para probar el efecto que surten
los helados en los pacientes oncológicos. Aunque la investigación sigue en
marcha en las unidades de hospitalización oncológica del Consorcio
Hospitalario de Tarrasa y el Parque Taulí de Sabadell, empiezan a apreciarse los
beneficios de este exquisito postre en el ánimo de los enfermos, medido en
encuestas de satisfacción.
Esta idea surgió tras el encuentro que mantuvo Casas con Angelo Corvito,
heladero artesano de origen italiano, quien le hizo apreciar el alto valor nutricional
de los helados (poseen proteínas, hidratos de carbono, vitaminas y
sales minerales). Los 180 gramos de helado artesano adaptado (con una textura
más cremosa y menos fría de lo habitual) que los pacientes oncológicos
ingieren cada día suponen una fuente de energía para los pacientes, que también
agradecen este nuevo placer en su menú nutricional.
Las repercusiones de la alimentación sobre la salud se conocen
desde la época de Hipócrates, el primer médico que describe y pone nombre
al cáncer, que afirmaba cuatro siglos antes de Cristo que “el vigor del hambre
puede influir violentamente en la constitución del hombre, debilitándolo, haciéndolo
enfermar e, incluso, sucumbir”.
Antes de adentrarnos en materia, cabe matizar que un paciente está malnutrido cuando presenta un cuadro clínico caracterizado por un desequilibrio entre la ingesta de nutrientes y las necesidades nutricionales básicas.
Si este desequilibrio es negativo, se habla de desnutrición. En el caso del enfermo oncológico, aparecen la malnutrición y la desnutrición.
La malnutrición asociada al cáncer es un factor de mal pronóstico, independientemente del tumor, tanto para la supervivencia como para la respuesta al tratamiento.
Magdalena García Huerta, del Servicio de Endocrinología y Nutrición
del Hospital Universitario La Paz, de Madrid, nos explica que “una mala
alimentación en el enfermo neoplásico produce disfunción inmunológica y deficiencias
en zinc, hierro, vitaminas A, B6, B12, D y E y ácido fólico, así como alteraciones
lipídicas (exceso de colesterol y ácidos grasos libres y déficit de ácidos
grasos esenciales)”. El porcentaje de enfermos oncológicos
que presenta malnutrición oscila entre el 15 y el 40 por ciento en el
momento de realizar el diagnóstico, aunque estas cifras aumentan hasta un 80
por ciento en los casos de enfermedad avanzada.
El enfermo neoplásico presenta malnutrición como consecuencia de la biología tumoral maligna y del tratamiento oncológico.
El cáncer produce disminución de la ingesta de forma directa, interfiriendo de forma mecánica con el tránsito normal del tubo digestivo, o de forma indirecta, a través de la secreción de sustancias que actúan sobre receptores periféricos o sobre el hipotálamo.
Los tumores localizados en el tubo digestivo (faringe, esófago, estómago y
páncreas) provocan obstrucción de forma directa o sensación de saciedad
precoz por limitación de la capacidad gástrica. Un efecto similar se observa en
tumores que derivan de otros órganos, pero que producen una comprensión
extrínseca del estómago. Es típico el desplazamiento gástrico que ocasionan
algunos de los síntomas de las metástasis hepáticas, así como la obstrucción
intestinal asociada a los implantes peritoneales de los tumores ováricos, pancreáticos
o gástricos.
Los tumores de cabeza y cuello, esófago, estómago, páncreas, colon y
recto son los que causan una malnutrición más severa, mientras que el cáncer
de mama, próstata, pulmón, algunos linfomas y la leucemia casi no alteran el
estado nutricional de los enfermos.
En este sentido, García Huerta nos comenta que “en casos de cánceres gástricos y de páncreas, la pérdida de peso es del 10 por ciento en un tercio de los pacientes, teniendo una incidencia de caquexia [léase más adelante] de entre el 83 y el 87 por ciento”.
En un estudio retrospectivo del Eastern Cooperative Oncology Group
(ECOG), realizado en 3.047 pacientes que iban a iniciar sesiones de quimioterapia,
se observó que el 50 por ciento ya habían perdido peso antes del tratamiento,
y que un 15 por ciento habían perdido más del 10 por ciento de su
peso habitual.
La malnutrición conlleva una mayor morbilidad en los enfermos neoplásicos, por lo que es prioritario realizar una adecuada valoración de su estado nutricional, tanto en el diagnóstico de la enfermedad como de forma seriada, en distintos momentos de la evolución del cáncer.
La especialista del Servicio de Endocrinología y Nutrición del Hospital La
Paz nos explica los diferentes métodos para identificar a pacientes con malnutrición
o con un riesgo significativo de complicaciones: “Estos procedimientos
pueden basarse en parámetros antropométricos (peso, talla, índice de masa
corporal -IMC-, pliegues cutáneos y circunferencia muscular del brazo), en la
medición de proteínas plasmáticas (albúmina, transferrina) y en la Valoración
Global Subjetiva (VGS)”.
La Valoración Global Subjetiva Generada por el Paciente (VGS-GP) es el test de valoración del estado nutricional más utilizado en la actualidad, al contar con una buena relación costeefectividad al poder ser aplicable por cualquier miembro del personal sanitario con un nivel mínimo de adiestramiento y, sobre todo, al ayudar en la toma de decisión sobre el tratamiento nutricional más adecuado.
Se trata de un método diseñado por Detsky y col. en 1987 en el Hospital General de
Toronto, basado en la historia clínica del enfermo y en su exploración física.
“Este método es sensible, específico y presenta poca variabilidad entre
observadores, clasificando a los pacientes en tres grupos: categoría A
(adecuado estado nutricional), categoría B (sospecha de malnutrición o malnutrición
moderada) y categoría C (malnutrición severa)”, destaca Magdalena
García Huerta.
La desnutrición también disminuye considerablemente la calidad de vida
de los enfermos neoplásicos, sobre todo por su influencia sobre la fuerza
muscular y la sensación de debilidad y de cansancio o astenia, así como por el
impacto psicológico, que puede inducir síntomas depresivos. Todas estas
situaciones complican el cuadro y disminuyen la autonomía del enfermo, lo
que alarga su estancia en el hospital.
El síndrome anorexia-caquexia es una manifestación multiorgánica que
provoca numerosas complicaciones fisiológicas y funcionales. El término
caquexia deriva del griego “kakos” y “hexis”, que significa “mal estado o
condición”. Los términos caquexia y malnutrición siempre van asociados, ya
que siempre que hay caquexia aparece la malnutrición.
La caquexia se caracteriza por una pérdida progresiva de peso de forma
involuntaria, acompañada de anorexia (disminución en la ingesta), astenia
(debilidad y letargo), atrofia muscular y alteraciones inmunes y de la capacidad
de atención y concentración. A menudo aparecen náuseas, alteraciones del
gusto y olfato, anemia, sensación de saciedad precoz y estreñimiento.
La caquexia tiene sus orígenes en dos aspectos fundamentales: el aumento
de demanda calórica por la presencia del tumor y la malnutrición debida a la
anorexia. Los factores desencadenantes del síndrome pueden ser de origen
tumoral o humoral (citoquinas producidas por el huésped en respuesta al
tumor -o por el propio tumor- y alteraciones hormonales).
El síndrome de la caquexia cancerosa alcanza aproximadamente al 70 por
ciento de los pacientes en un estadio avanzado de la enfermedad y es directamente
responsable de la muerte de, al menos, el 22 por ciento de los pacientes
oncológicos. La caquexia afecta a numerosos órganos tejidos del cuerpo como el músculoesquelético (representa casi el 40 por ciento de nuestro peso), lo que provoca pérdida de fuerza y disminución de resistencia al esfuerzo; la piel (adelgazamiento y pérdida de elasticidad, facilidad para contraer úlceras decúbito, cabello ralo y seco o uñas quebradizas); corazón (disminuye la masa cardiaca y el índice cardiaco) o el hígado.
También afecta al riñón, al aparato respiratorio y gastrointestinal y a los sistemas nervioso e inmunitario.
Actualmente, existen multitud de armas terapéuticas para combatir el síndrome
anorexia-caquexia. García Huerta nos explica que “los medicamentos más recomendables
son los ácidos grasos omega-3, que son moléculas fundamentalmente
anticatabólicas que impiden la degradación de las proteínas musculares; la leucina,
un aminoácido esencial que estimula la síntesis proteica a nivel muscular e inhibe
el sistema proteolítico (degradación muscular), y la metionina, otro aminoácido
esencial que consigue potenciar el efecto de la leucina”.
Como fármacos estimulantes del apetito se utilizan los corticosteroides,
los cannabinoides (la marihuana y sus derivados estimulan el apetito, aunque
no hay estudios que permitan recomendar su utilización) y los progestágenos.
Como fármacos procinéticos (profilaxis de náuseas y vómitos) se utiliza fundamentalmente la metoclopramida, y como fármacos inhibidores del catabolismo
están el sulfato de hidracina, la pentoxifilina y la talidomida, entre otros.
También se estudian nuevas alternativas terapéuticas como la melatonina,
una de las sustancias que cuenta con mayor futuro potencial en el tratamiento
de la caquexia tumoral y cuyo mecanismo de acción se desarrolla a través de
la inhibición de las citoquinas. La dieta oral en algunos pacientes
con cáncer puede plantear serias dificultades, por lo que se recomienda la nutrición
artificial, bien por vía enteral o parenteral.
La nutrición enteral puede definirse como el aporte de nutrientes por vía
digestiva, ya sea a través de sondas nasoentéricas, catéteres de ostomía (abertura
en el abdomen) o vía oral a intervalos regulares, siempre que la cantidad que
debe administrarse supere las 1.000 kcal o 40 gramos de proteínas al día. Se
trata de una técnica de bajo coste, más fisiológica y más fácil de mantener.
Para entender bien todos estos conceptos, cabe destacar que existen dos
vías de acceso al tracto gastrointestinal: nasal (vía naso-gástrica, naso-yeyunal y
naso-duodenal) y ostomías (gastrostomía y yeyunostomía).
La vía nasogástrica es el método más simple y consiste en la administración
de los nutrientes a través de sondas fabricadas en silicona o poliuretano.
Esta alternativa es recomendada para nutriciones de no más de seis semanas y
su principal inconveniente es que resulta molesta para el paciente. Por su parte,
la gastrostomía supone el establecimiento de una fístula gastro-cutánea dirigida
sobre tubo y se recomienda para pacientes que requieren nutrición enteral
prolongada.
La nutrición parenteral consiste en administrar nutrientes al organismo por
vía extradigestiva, es decir, a través del torrente sanguíneo, sin el proceso digestivo y filtro hepático natural. Además de que supone una elevada carga asistencial y un coste económico considerable, este tipo de nutrición conlleva complicaciones por la elevada incidencia de infecciones y los problemas atribuibles al exceso o déficit de nutrientes. De hecho, e de los 40 estudios realizados hasta la un tumor fecha, se concluye que el beneficio de esta técnica en pacientes oncológicos
es muy dudoso. La nutrición parenteral está indicada en pacientes cuyo tracto gastrointestinal no es utilizable para la administración, digestión o absorción de nutrientes durante un periodo superior a 5-7 días, o cuando el tubo digestivo es utilizable pero se desea mantener en reposo por razones terapéuticas.
Como alternativa a la alimentación tradicional, surge la Alimentación Básica
Adaptada (ABA), que ofrece una serie de productos que se adaptan a las necesidades
del paciente en nutrientes y textura, es de fácil preparación, mantiene el
aspecto de “plato hecho en casa” y tiene un sabor identificable con la alimentación
casera. Actualmente, existen preparados en forma de purés, listos para su consumo,
o en forma de puré instantáneo, liofilizado, presentado en polvo para ser
reconstituido con caldo, agua, leche y un poco de aceite. También existen preparados
a base de cereales y frutas, con textura suave y homogénea, así como postres
de frutas listas para consumir en forma de compota instantánea para mezclar
con agua o zumo.
El oncólogo y escritor Francesc Casas puso en marcha en diciembre del
año pasado un estudio de un año de duración para probar el efecto que surten
los helados en los pacientes oncológicos. Aunque la investigación sigue en
marcha en las unidades de hospitalización oncológica del Consorcio
Hospitalario de Tarrasa y el Parque Taulí de Sabadell, empiezan a apreciarse los
beneficios de este exquisito postre en el ánimo de los enfermos, medido en
encuestas de satisfacción.
Esta idea surgió tras el encuentro que mantuvo Casas con Angelo Corvito,
heladero artesano de origen italiano, quien le hizo apreciar el alto valor nutricional
de los helados (poseen proteínas, hidratos de carbono, vitaminas y
sales minerales). Los 180 gramos de helado artesano adaptado (con una textura
más cremosa y menos fría de lo habitual) que los pacientes oncológicos
ingieren cada día suponen una fuente de energía para los pacientes, que también
agradecen este nuevo placer en su menú nutricional.
lunes, 20 de abril de 2015
Cansancio y debilidad en el paciente en tratamiento oncológico. Recomendaciones del NCI
Cansancio y debilidad
(Available in English, Fatigue—Feeling Weak and Very Tired: Managing Chemotherapy Side Effects)
Diga a su doctor o enfermera si:
* No puede hacer sus actividades normales.
* Siente mucho cansancio aun después de haber descansado o dormido
“Estaba tan cansada. Me costaba mucho trabajo hacer hasta las cosas más sencillas.
Mi enfermera me dijo que tratara de mantenerme activa. Descubrí que caminar un poco por las mañanas me daba más energía durante el día”. —Josefina
¿Por qué siento tanto cansancio?
La quimioterapia por sí sola puede cansarle. Otras cosas también pueden causarle cansancio, tales como:
* la anemia (tener una cantidad baja de glóbulos rojos en la sangre)
* la depresión
* el dolor
* algunas medicinas
* los problemas para dormir
Haga un plan para sentir menos cansancio. Haga menos cosas. Deje que otros le ayuden.
* Haga primero las actividades más importantes.
* Pida ayuda a los demás.
* Tome tiempo libre de su trabajo o trabaje menos horas.
Consejos para los efectos de la quimioterapia
Coma sano y beba mucho líquido.
* Prepare alimentos saludables cuando se sienta bien. Congélelos para comerlos después.
* Coma 5 ó 6 comidas pequeñas durante el día (en vez de 3 comidas grandes). Esto le ayudará a mantener sus fuerzas.
* La mayoría de las personas necesitan beber por lo menos 8 vasos de agua al día. Vaso de 230 ml
Mantenga el agua cerca de usted y tome unos tragos durante el día.
Mantenga tanta actividad como sea posible.
* Trate de hacer ejercicios todos los días. Aun 15 a 30 minutos al día pueden darle energía.
* Camine o haga ejercicios en una bicicleta estacionaria cada día.
* Hable con su doctor o enfermera sobre otros ejercicios que puedan ayudarle. Estirarse, hacer
“Tai Chi” ayudan a algunas personas.
Tome tiempo para descansar.
* Preste atención a su cuerpo. Descanse cuando sienta cansancio.
* Trate de tomar siestas cortas (de 1 hora o menos) durante el día.
* Póngase un horario para ir a la cama. Báñese o escuche música antes de dormir para relajarse.
* Duerma por lo menos 8 horas cada noche.
Preguntas para su doctor
o enfermera:
1. ¿De qué problemas debo avisarles?
2. ¿Qué medicinas o qué tratamientos pueden
ayudarme?
3. ¿Cuáles alimentos y bebidas me hacen bien?
4. ¿Cuánto líquido debo beber cada día?
5. ¿Cuáles ejercicios pueden ayudar a que me
sienta mejor?
(Available in English, Fatigue—Feeling Weak and Very Tired: Managing Chemotherapy Side Effects)
Diga a su doctor o enfermera si:
* No puede hacer sus actividades normales.
* Siente mucho cansancio aun después de haber descansado o dormido
“Estaba tan cansada. Me costaba mucho trabajo hacer hasta las cosas más sencillas.
Mi enfermera me dijo que tratara de mantenerme activa. Descubrí que caminar un poco por las mañanas me daba más energía durante el día”. —Josefina
¿Por qué siento tanto cansancio?
La quimioterapia por sí sola puede cansarle. Otras cosas también pueden causarle cansancio, tales como:
* la anemia (tener una cantidad baja de glóbulos rojos en la sangre)
* la depresión
* el dolor
* algunas medicinas
* los problemas para dormir
Haga un plan para sentir menos cansancio. Haga menos cosas. Deje que otros le ayuden.
* Haga primero las actividades más importantes.
* Pida ayuda a los demás.
* Tome tiempo libre de su trabajo o trabaje menos horas.
Consejos para los efectos de la quimioterapia
Coma sano y beba mucho líquido.
* Prepare alimentos saludables cuando se sienta bien. Congélelos para comerlos después.
* Coma 5 ó 6 comidas pequeñas durante el día (en vez de 3 comidas grandes). Esto le ayudará a mantener sus fuerzas.
* La mayoría de las personas necesitan beber por lo menos 8 vasos de agua al día. Vaso de 230 ml
Mantenga el agua cerca de usted y tome unos tragos durante el día.
Mantenga tanta actividad como sea posible.
* Trate de hacer ejercicios todos los días. Aun 15 a 30 minutos al día pueden darle energía.
* Camine o haga ejercicios en una bicicleta estacionaria cada día.
* Hable con su doctor o enfermera sobre otros ejercicios que puedan ayudarle. Estirarse, hacer
“Tai Chi” ayudan a algunas personas.
Tome tiempo para descansar.
* Preste atención a su cuerpo. Descanse cuando sienta cansancio.
* Trate de tomar siestas cortas (de 1 hora o menos) durante el día.
* Póngase un horario para ir a la cama. Báñese o escuche música antes de dormir para relajarse.
* Duerma por lo menos 8 horas cada noche.
Preguntas para su doctor
o enfermera:
1. ¿De qué problemas debo avisarles?
2. ¿Qué medicinas o qué tratamientos pueden
ayudarme?
3. ¿Cuáles alimentos y bebidas me hacen bien?
4. ¿Cuánto líquido debo beber cada día?
5. ¿Cuáles ejercicios pueden ayudar a que me
sienta mejor?
Mucositis y esofagitis en el paciente en tratamiento oncológico. Recomendaciones SEOM
ÚLCERAS O LLAGAS EN LA BOCA
CONSEJOS PARA EL TRATAMIENTO
DE LAS ÚLCERAS O LLAGAS EN LA BOCA
• Fraccionar las comidas en tomas pequeñas y frecuentes.
• Evitar alimentos que se pegan al paladar; ingerir bocados
pequeños y masticarlos completamente.
• Incluir alimentos fáciles de ingerir con alto valor energético:
helado de mantecado, batidos enriquecidos, etc.
• Tener alimentos infantiles a mano que pueden solucionar
situaciones concretas.
• Comer los alimentos a temperatura ambiente o fríos
para disminuir el dolor.
• Evitar los alimentos secos (tostadas, frutos secos),especias fuertes (pimienta,
pimentón), los sabores ácidos (limón, kivi), amargos,muy dulces o muy salados.
• Usar salsas, nata, mantequilla o gelatina para conseguir
la consistencia deseada y facilitar así la deglución.
• Pueden ser útiles los espesantes comerciales y el agua
gelificada para conseguir la consistencia deseada.
• Para reducir el tamaño de los alimentos, utilizar el chino,
la trituradora y la licuadora. Si esta preparación conlleva
una pérdida de proteínas, se puede añadir a la preparación
una clara de huevo.
• Se recomiendan comidas que incluyan patatas, papaya,
miel, salvia. Tienen virtudes de efecto antiséptico, depurativo,
etc.
• Utilizar una pajilla para ingerir determinados alimentos.
• Beber agua durante todo el día.
• Dejar escapar el gas de los refrescos gaseosos.
• Evitar las bebidas alcohólicas, cigarrillos, pipa y cualquier
forma de tabaco.
• Preguntar a su médico o enfermera sobre los enjuagues
bucales para hacer gárgaras.
• Hacer enjuagues con miel diluida en agua o con infusiones
de tomillo, salvia, manzanilla, bicarbonato (una cucharada
de las de café diluida en medio vaso de agua).
• Antes de las comidas, dejar en la boca agua muy fría o hielo
triturado para adormecer el dolor y poder ingerir mejor.
• Si hay dificultades para tragar pastillas o cápsulas, preguntar
al médico o enfermera si se pueden triturar o si están
disponibles en jarabes.
• Si la temperatura es igual o superior a 38 oC o si se tiene
dolor al ingerir alimentos líquidos, avisar al médico o
enfermera.
MENÚS RECOMENDADOS EN CASO DE MUCOSITIS
Desayuno-merienda
• En ayunas, tomar una cucharada de miel pura, se ensaliva
bien y se espera como mínimo 1 hora antes del desayuno.
• Leche entera, leche de soja, leche de almendra.
• Galletas, magdalenas, melindros, bizcochos caseros mojados
en leche.
• Papilla de cereales con leche.
• Papilla de frutas con una cucharada de levadura de cerveza.
• Yogur con una cucharada de levadura de cerveza y miel.
• Pan de molde con: manteca de cacahuete, queso fundido,
mantequilla con salmón, mantequilla con jamón de york,
leche condensada, zumos de papaya, patata, etc.
Comida-cena
PRIMEROS PLATOS
• Espárragos con mayonesa ligera.
• Calabacín, patata y zanahoria al vapor o hervida, aliñada
con aceite de oliva virgen.
• Patatas al horno o hervidas con mayonesa de aguacate.
• Puré de patata con una cucharada de levadura de cerveza.
• Crema de espinacas.
• Crema de boniato.
• Crema de calabaza con salvia.
• Crema de legumbres: garbanzos, lentejas con arroz, judías
secas, guisantes, etc.
• Pasta italiana con salsa suave o aliñada con albahaca y
aceite de oliva virgen.
• Sopas (de carne, pescado, vegetal) con fideos finos.
• Vichysoise fría.
• Soufflé de patatas.
• Mousse de escalivada.
• Flan de judías.
SEGUNDOS PLATOS
• Croquetas de queso, de bacalao, patata.
• Canalones de espinacas, pescado, carne.
• Pastel de patata.
• Gelatina de pescado, de pollo.
• Brandada de bacalao.
• Filete de ternera con verduras y queso (pasado todo por
el chino).
• Merluza con verduras (pasado todo por el chino).
POSTRES
• Plátano maduro, papaya, mango, fruta en almíbar, flan, yogur,
requesón con miel, helado, sorbetes, natillas, compota
de manzana, pera hervida, gelatina de frutas.
RECETAS ACONSEJADAS PARA PACIENTES
CON MUCOSITIS Y ESOFAGITIS
CREMA DE BONIATO
Ingredientes: 1 boniato, 1 yema de huevo, 1 cucharadita de
miel y un poco de leche.
Preparación: Ponga el boniato al vapor y cuando esté tierno
retírelo y quítele la piel. Páselo por la batidora con un poco
de leche y la yema de huevo. Finalmente, añada la miel.
CREMA DE CALABAZA CON SALVIA
Ingredientes: 200 gramos de calabaza, 1 cucharada de queso
parmesano o queso de oveja rallado, 4 hojas de salvia, 1/2 ramita
de romero, 1/2 ajo y 1 cucharada de aceite de oliva virgen.
Preparación: Corte la calabaza a dados y cuézala al vapor
hasta que esté tierna. Triture muy finas las hierbas aromáticas
y póngalas junto al ajo y el aceite en una sartén honda.
Deje cocer a fuego lento unos minutos, después añada
la calabaza, mézclela bien, aplastando la calabaza con un
tenedor, y déjela a fuego lento unos 5 minutos. Retírela del
fuego y pásela por la batidora.
MAYONESA DE AGUACATE
CON PATATAS
Ingredientes: 1 aguacate maduro, 1 patata mediana y mayonesa.
Preparación: Cueza al vapor
la patata sin pelar unos 20 minutos (pínchela con un cuchillo
para asegurarse de que está tierna). Cuando se enfríe la patata, pélela y trocéela.
Para la salsa, añada a la mayonesa (casera es mejor)la pulpa de un aguacate
maduro y mézclela bien. Vierta la salsa sobre la patata troceada.
SOUFFLÉ DE PATATAS
Ingredientes: 4 patatas de tamaño mediano, 1/2 vaso de
leche, 50 gramos de mantequilla, 2 huevos y sal.
Preparación: Ponga las patatas lavadas en agua fría con sal.
Déjelas hervir y cocer. Quíteles la piel y aplástelas. Añada
la mantequilla, la leche y la sal. Bata la mezcla con un batidor
y añada una a una las yemas de los huevos sin dejar
de batir. Incorpore luego las claras batidas a punto de nieve
muy firme y mézclelo todo cuidadosamente. Engrase con
mantequilla una fuente de soufflé. Vierta la mezcla y ponga
la fuente en el horno. Deje que se dore.
VICHYSOISE
Ingredientes: 250 gramos de puerros cortados a rodajitas
finas, 400 gramos de patatas cortadas a rodajas, una cucharada
de perejil picado, 40 gramos de margarina, 150 gramos
de nata o 75 gramos de crema de leche.
Preparación: En un cazo con la margarina, rehogue los
puerros y luego añada las patatas. Sazone con sal y añada
un litro y cuarto de agua caliente, dejando hervir durante
30 minutos. Páselo después por un colador chino. Ya
en su punto, agregue la nata o crema de leche y el perejil
picado. Póngalo en nevera hasta el momento de servir. En
las tazas de consomé, si lo desea, se pueden poner cubitos
de hielo.
MOUSSE DE ESCALIVADA
Ingredientes: 2 pimientos grandes, 2 berenjenas grandes,
200 mL de crema de leche, 125 mL de leche, 5 huevos y sal.
Preparación: Ponga los pimientos y las berenjenas sin pelar
y lavados en una fuente en el horno con el gratinador
encendido. Mientras se asan, deles alguna vuelta hasta que
estén bien asados. Retire la fuente y tápela con un trapo
húmedo hasta que se enfríen y se puedan pelar mejor. Una
vez limpios, tritúrelos con la batidora añadiendo al mismo
tiempo la mitad de la crema de leche; después, termine de
echarla toda y a continuación añada la leche hirviendo previamente
mezclada con los huevos ligeramente batidos sazonados
con sal. Eche toda la mezcla en un molde previamente
forrado con papel en el fondo y engrasado. Póngala
en el horno al baño maría unos 50 o 60 minutos. Una vez
cocido, déjelo enfriar para desmoldarlo.
FLAN DE JUDÍAS
Ingredientes: 1 kilo de judías verdes que estén tiernas, 1
vaso de leche, 1 vaso de nata líquida, 4 huevos, 1 puerro
pequeño, mantequilla y sal.
Preparación: Lave y pique las judías y el puerro. Ponga
todo al vapor durante unos 10 minutos. En una sartén
grande, ponga una cucharada de mantequilla y cuando se
caliente rehogue en ella el puerro y las judías con un poco
de sal.
En un bol bata bien los huevos y añada la leche y la nata.
Engrase el molde del flan con mantequilla. Vierta el rehogado
de verduras y añada la mezcla batida. Cuézalo durante
1 hora al baño maría en el horno, compruebe que está
cuajado pinchándolo con una aguja. Desmolde sobre una
fuente justo antes de servir, acompañado de una salsa si lo
desea. Es preferible tomarlo frío.
CROQUETAS DE QUESO
Ingredientes: 1/2 kilo de patatas, 25 gramos de mantequilla,
125 gramos de queso, 2 huevos, sal, pan rallado muy
fino y aceite de oliva virgen.
Preparación: Cueza las patatas sin pelar en agua salada.
Una vez cocidas, pélelas y aplástelas con un tenedor hasta
obtener un puré muy fino. Ralle el queso y añádalo al
puré de patatas, así como la mantequilla derretida. Mézclelo
todo bien. Separe la yema de la clara de un huevo
e incorpórela a la masa que tiene en la cazuela, mezclándola
bien. Cuando la pasta quede homogénea, eche
la clara que ha batido previamente a punto de nieve.
Únalo todo cuidadosamente. En un plato bata el huevo
restante y en otro ponga el pan rallado. Con la pasta que
tenemos en la cazuela se forman las croquetas, se mojan
en el huevo batido y se rebozan con pan rallado. Se
fríen en aceite bien caliente. Deje enfriar las croquetas
antes de comerlas.
HELADO DE VAINILLA
Ingredientes: 350 mL de leche, 1 rama de vainilla, 100 gramos
de miel, 2 yemas de huevo y 200 gramos de nata
batida.
Preparación: Vier ta la leche en un cazo pequeño. Corte
la vainilla a lo largo. Saque las semillas y eche la rama
y las semillas en la leche. Bata en una fuente la miel y
las yemas de huevo haciendo espuma hasta que la
masa tome color amarillo y haga hilos. Posteriormente,hierva la leche que está en
el bote al baño maría. Cuando suba, retírela del fuego.
Separe la rama de vainilla y vierta lentamente la leche en la yema del huevo removiendo deprisa. Vuelva a verter todo en el cazo y déjelo
calentar hasta punto de ebullición. Añada la nata batida y
después deje enfriar la masa en un baño de agua fría.
Vierta la masa preparada en un recipiente metálico que
se ha congelado previamente y métalo en el congelador.
Remueva a fondo una vez cada hora al principio, y después más a menudo.
SORBETE DE HIERBAS
Ingredientes: 220 mL de té de hierbas fuertes, 50 gramos
de miel y 2 claras de huevo.
Preparación: Disuelva la miel en el té; échela en la sorbetera
o recipiente metálico y déjela congelar un poco. Bata
las claras a punto de nieve y únalas a la masa del té de hierbas.
Congélela hasta obtener la consistencia deseada.
ZUMOS
Se puede mezclar los zumos con agua si se prefiere. Es
aconsejable licuar cada fruta o verdura por separado y mezclar
los diferentes zumos poco a poco.
Ingredientes: 50 gramos de patatas, 3 tomates.
Ingredientes: 1/2 papaya, 1 melocotón.
Ingredientes: 1/2 papaya, 1 manzana.
Ingredientes: 2 zanahorias grandes, 125 gramos de col
blanca.
CONSEJOS PARA EL TRATAMIENTO
DE LAS ÚLCERAS O LLAGAS EN LA BOCA
• Fraccionar las comidas en tomas pequeñas y frecuentes.
• Evitar alimentos que se pegan al paladar; ingerir bocados
pequeños y masticarlos completamente.
• Incluir alimentos fáciles de ingerir con alto valor energético:
helado de mantecado, batidos enriquecidos, etc.
• Tener alimentos infantiles a mano que pueden solucionar
situaciones concretas.
• Comer los alimentos a temperatura ambiente o fríos
para disminuir el dolor.
• Evitar los alimentos secos (tostadas, frutos secos),especias fuertes (pimienta,
pimentón), los sabores ácidos (limón, kivi), amargos,muy dulces o muy salados.
• Usar salsas, nata, mantequilla o gelatina para conseguir
la consistencia deseada y facilitar así la deglución.
• Pueden ser útiles los espesantes comerciales y el agua
gelificada para conseguir la consistencia deseada.
• Para reducir el tamaño de los alimentos, utilizar el chino,
la trituradora y la licuadora. Si esta preparación conlleva
una pérdida de proteínas, se puede añadir a la preparación
una clara de huevo.
• Se recomiendan comidas que incluyan patatas, papaya,
miel, salvia. Tienen virtudes de efecto antiséptico, depurativo,
etc.
• Utilizar una pajilla para ingerir determinados alimentos.
• Beber agua durante todo el día.
• Dejar escapar el gas de los refrescos gaseosos.
• Evitar las bebidas alcohólicas, cigarrillos, pipa y cualquier
forma de tabaco.
• Preguntar a su médico o enfermera sobre los enjuagues
bucales para hacer gárgaras.
• Hacer enjuagues con miel diluida en agua o con infusiones
de tomillo, salvia, manzanilla, bicarbonato (una cucharada
de las de café diluida en medio vaso de agua).
• Antes de las comidas, dejar en la boca agua muy fría o hielo
triturado para adormecer el dolor y poder ingerir mejor.
• Si hay dificultades para tragar pastillas o cápsulas, preguntar
al médico o enfermera si se pueden triturar o si están
disponibles en jarabes.
• Si la temperatura es igual o superior a 38 oC o si se tiene
dolor al ingerir alimentos líquidos, avisar al médico o
enfermera.
MENÚS RECOMENDADOS EN CASO DE MUCOSITIS
Desayuno-merienda
• En ayunas, tomar una cucharada de miel pura, se ensaliva
bien y se espera como mínimo 1 hora antes del desayuno.
• Leche entera, leche de soja, leche de almendra.
• Galletas, magdalenas, melindros, bizcochos caseros mojados
en leche.
• Papilla de cereales con leche.
• Papilla de frutas con una cucharada de levadura de cerveza.
• Yogur con una cucharada de levadura de cerveza y miel.
• Pan de molde con: manteca de cacahuete, queso fundido,
mantequilla con salmón, mantequilla con jamón de york,
leche condensada, zumos de papaya, patata, etc.
Comida-cena
PRIMEROS PLATOS
• Espárragos con mayonesa ligera.
• Calabacín, patata y zanahoria al vapor o hervida, aliñada
con aceite de oliva virgen.
• Patatas al horno o hervidas con mayonesa de aguacate.
• Puré de patata con una cucharada de levadura de cerveza.
• Crema de espinacas.
• Crema de boniato.
• Crema de calabaza con salvia.
• Crema de legumbres: garbanzos, lentejas con arroz, judías
secas, guisantes, etc.
• Pasta italiana con salsa suave o aliñada con albahaca y
aceite de oliva virgen.
• Sopas (de carne, pescado, vegetal) con fideos finos.
• Vichysoise fría.
• Soufflé de patatas.
• Mousse de escalivada.
• Flan de judías.
SEGUNDOS PLATOS
• Croquetas de queso, de bacalao, patata.
• Canalones de espinacas, pescado, carne.
• Pastel de patata.
• Gelatina de pescado, de pollo.
• Brandada de bacalao.
• Filete de ternera con verduras y queso (pasado todo por
el chino).
• Merluza con verduras (pasado todo por el chino).
POSTRES
• Plátano maduro, papaya, mango, fruta en almíbar, flan, yogur,
requesón con miel, helado, sorbetes, natillas, compota
de manzana, pera hervida, gelatina de frutas.
RECETAS ACONSEJADAS PARA PACIENTES
CON MUCOSITIS Y ESOFAGITIS
CREMA DE BONIATO
Ingredientes: 1 boniato, 1 yema de huevo, 1 cucharadita de
miel y un poco de leche.
Preparación: Ponga el boniato al vapor y cuando esté tierno
retírelo y quítele la piel. Páselo por la batidora con un poco
de leche y la yema de huevo. Finalmente, añada la miel.
CREMA DE CALABAZA CON SALVIA
Ingredientes: 200 gramos de calabaza, 1 cucharada de queso
parmesano o queso de oveja rallado, 4 hojas de salvia, 1/2 ramita
de romero, 1/2 ajo y 1 cucharada de aceite de oliva virgen.
Preparación: Corte la calabaza a dados y cuézala al vapor
hasta que esté tierna. Triture muy finas las hierbas aromáticas
y póngalas junto al ajo y el aceite en una sartén honda.
Deje cocer a fuego lento unos minutos, después añada
la calabaza, mézclela bien, aplastando la calabaza con un
tenedor, y déjela a fuego lento unos 5 minutos. Retírela del
fuego y pásela por la batidora.
MAYONESA DE AGUACATE
CON PATATAS
Ingredientes: 1 aguacate maduro, 1 patata mediana y mayonesa.
Preparación: Cueza al vapor
la patata sin pelar unos 20 minutos (pínchela con un cuchillo
para asegurarse de que está tierna). Cuando se enfríe la patata, pélela y trocéela.
Para la salsa, añada a la mayonesa (casera es mejor)la pulpa de un aguacate
maduro y mézclela bien. Vierta la salsa sobre la patata troceada.
SOUFFLÉ DE PATATAS
Ingredientes: 4 patatas de tamaño mediano, 1/2 vaso de
leche, 50 gramos de mantequilla, 2 huevos y sal.
Preparación: Ponga las patatas lavadas en agua fría con sal.
Déjelas hervir y cocer. Quíteles la piel y aplástelas. Añada
la mantequilla, la leche y la sal. Bata la mezcla con un batidor
y añada una a una las yemas de los huevos sin dejar
de batir. Incorpore luego las claras batidas a punto de nieve
muy firme y mézclelo todo cuidadosamente. Engrase con
mantequilla una fuente de soufflé. Vierta la mezcla y ponga
la fuente en el horno. Deje que se dore.
VICHYSOISE
Ingredientes: 250 gramos de puerros cortados a rodajitas
finas, 400 gramos de patatas cortadas a rodajas, una cucharada
de perejil picado, 40 gramos de margarina, 150 gramos
de nata o 75 gramos de crema de leche.
Preparación: En un cazo con la margarina, rehogue los
puerros y luego añada las patatas. Sazone con sal y añada
un litro y cuarto de agua caliente, dejando hervir durante
30 minutos. Páselo después por un colador chino. Ya
en su punto, agregue la nata o crema de leche y el perejil
picado. Póngalo en nevera hasta el momento de servir. En
las tazas de consomé, si lo desea, se pueden poner cubitos
de hielo.
MOUSSE DE ESCALIVADA
Ingredientes: 2 pimientos grandes, 2 berenjenas grandes,
200 mL de crema de leche, 125 mL de leche, 5 huevos y sal.
Preparación: Ponga los pimientos y las berenjenas sin pelar
y lavados en una fuente en el horno con el gratinador
encendido. Mientras se asan, deles alguna vuelta hasta que
estén bien asados. Retire la fuente y tápela con un trapo
húmedo hasta que se enfríen y se puedan pelar mejor. Una
vez limpios, tritúrelos con la batidora añadiendo al mismo
tiempo la mitad de la crema de leche; después, termine de
echarla toda y a continuación añada la leche hirviendo previamente
mezclada con los huevos ligeramente batidos sazonados
con sal. Eche toda la mezcla en un molde previamente
forrado con papel en el fondo y engrasado. Póngala
en el horno al baño maría unos 50 o 60 minutos. Una vez
cocido, déjelo enfriar para desmoldarlo.
FLAN DE JUDÍAS
Ingredientes: 1 kilo de judías verdes que estén tiernas, 1
vaso de leche, 1 vaso de nata líquida, 4 huevos, 1 puerro
pequeño, mantequilla y sal.
Preparación: Lave y pique las judías y el puerro. Ponga
todo al vapor durante unos 10 minutos. En una sartén
grande, ponga una cucharada de mantequilla y cuando se
caliente rehogue en ella el puerro y las judías con un poco
de sal.
En un bol bata bien los huevos y añada la leche y la nata.
Engrase el molde del flan con mantequilla. Vierta el rehogado
de verduras y añada la mezcla batida. Cuézalo durante
1 hora al baño maría en el horno, compruebe que está
cuajado pinchándolo con una aguja. Desmolde sobre una
fuente justo antes de servir, acompañado de una salsa si lo
desea. Es preferible tomarlo frío.
CROQUETAS DE QUESO
Ingredientes: 1/2 kilo de patatas, 25 gramos de mantequilla,
125 gramos de queso, 2 huevos, sal, pan rallado muy
fino y aceite de oliva virgen.
Preparación: Cueza las patatas sin pelar en agua salada.
Una vez cocidas, pélelas y aplástelas con un tenedor hasta
obtener un puré muy fino. Ralle el queso y añádalo al
puré de patatas, así como la mantequilla derretida. Mézclelo
todo bien. Separe la yema de la clara de un huevo
e incorpórela a la masa que tiene en la cazuela, mezclándola
bien. Cuando la pasta quede homogénea, eche
la clara que ha batido previamente a punto de nieve.
Únalo todo cuidadosamente. En un plato bata el huevo
restante y en otro ponga el pan rallado. Con la pasta que
tenemos en la cazuela se forman las croquetas, se mojan
en el huevo batido y se rebozan con pan rallado. Se
fríen en aceite bien caliente. Deje enfriar las croquetas
antes de comerlas.
HELADO DE VAINILLA
Ingredientes: 350 mL de leche, 1 rama de vainilla, 100 gramos
de miel, 2 yemas de huevo y 200 gramos de nata
batida.
Preparación: Vier ta la leche en un cazo pequeño. Corte
la vainilla a lo largo. Saque las semillas y eche la rama
y las semillas en la leche. Bata en una fuente la miel y
las yemas de huevo haciendo espuma hasta que la
masa tome color amarillo y haga hilos. Posteriormente,hierva la leche que está en
el bote al baño maría. Cuando suba, retírela del fuego.
Separe la rama de vainilla y vierta lentamente la leche en la yema del huevo removiendo deprisa. Vuelva a verter todo en el cazo y déjelo
calentar hasta punto de ebullición. Añada la nata batida y
después deje enfriar la masa en un baño de agua fría.
Vierta la masa preparada en un recipiente metálico que
se ha congelado previamente y métalo en el congelador.
Remueva a fondo una vez cada hora al principio, y después más a menudo.
SORBETE DE HIERBAS
Ingredientes: 220 mL de té de hierbas fuertes, 50 gramos
de miel y 2 claras de huevo.
Preparación: Disuelva la miel en el té; échela en la sorbetera
o recipiente metálico y déjela congelar un poco. Bata
las claras a punto de nieve y únalas a la masa del té de hierbas.
Congélela hasta obtener la consistencia deseada.
ZUMOS
Se puede mezclar los zumos con agua si se prefiere. Es
aconsejable licuar cada fruta o verdura por separado y mezclar
los diferentes zumos poco a poco.
Ingredientes: 50 gramos de patatas, 3 tomates.
Ingredientes: 1/2 papaya, 1 melocotón.
Ingredientes: 1/2 papaya, 1 manzana.
Ingredientes: 2 zanahorias grandes, 125 gramos de col
blanca.
Infecciones y fiebre en el paciente en tratamiento oncológico. Consejos del NCI
Consejos para los efectos de la quimioterapia N.C.I.
National Cancer Institute
Infecciones
(Available in English, Infection:
Managing Chemotherapy Side Effects)
Hable con su doctor o enfermera antes de tomar cualquier medicina.
Esto incluye la aspirina, el paracetamol, o el ibuprofeno.
Hable con su doctor o enfermera antes de cualquier inyección o
vacuna.
Llame a su doctor de inmediato
si tiene:
l Fiebre de 38° C o más alta.
Pregunte cuántas veces al día debe tomar su temperatura.
l Escalofríos
l Tos o irritación de garganta
l Dolor de oído
l Dolor de cabeza o en los senos de la cara
(senos nasales)
l Cuello tenso o adolorido
l Orina nublada o con sangre
l Dolor o ardor al orinar
l Sarpullido (“rash”)
l Llagas o una capa blanca en la boca o en
la lengua
l Hinchazón o enrojecimiento en cualquier
parte del cuerpo. Si usted tiene un catéter,
esté alerta si tiene hinchazón o dolor en
el área junto al catéter.
l Otro:
__________________________________
¿Tiene algún otro cambio o síntoma
que no parece normal? No espere. Llame de inmediato a su doctor o
enfermera.
“Necesito alejarme de gérmenes que
pudieran enfermarme. Me lavo las manos
muy bien antes de comer. Cuando no
puedo lavarme las manos con agua, uso un
desinfectante de manos”. —Ana Esperanza
Siga los siguientes consejos para
evitar las infecciones:
Lávese bien las manos.
l Siempre lávese las manos:
• antes de cocinar o comer
• después de ir al baño
• después de estar en un sitio público.
l Lávese bien las manos con agua y jabón. Pida a las
personas que le rodean que también se laven bien las
manos.
l Use desinfectante de manos (“hand sanitizer”)
cuando no puede encontrar agua ni jabón.
Practique la limpieza.
l Cepille sus dientes después de las comidas y antes de
acostarse. Use un cepillo de dientes muy suave (“soft
toothbrush”).
l Si tiene un catéter, mantenga el área limpia y seca
alrededor del mismo. Hable con su enfermera para
saber cómo cuidar esta área.
Evite los microbios.
l Aléjese de las personas que están enfermas o
resfriadas. Trate de mantenerse lejos de ellas si puede.
l Lave frutas, vegetales, y verduras crudas.
l Lávese las manos con cuidado después de tocar
carne cruda. Cocine bien la carne antes de comerla.
l Trate de mantenerse lejos de personas que hayan
sido vacunadas recientemente contra la varicela,
la polio y el sarampión.
l Si tiene mascotas, trate que otra persona limpie la
suciedad.
Trate de no cortarse la piel.
l Use una afeitadora eléctrica y no una navaja de afeitar.
l Límpiese bien y con cuidado después de ir al baño.
Diga a su doctor o enfermera si el área del recto (ano)
le duele o sangra.
l No se apriete los barros ni las espinillas.
Preguntas para su doctor o enfermera:
1. ¿Por cuáles problemas debo llamarles?
2. ¿Qué otros pasos debo seguir para evitar infecciones?
3. ¿Cómo y cuándo debo tomarme la temperatura?
4. ¿Por cuáles problemas debo ir de inmediato a la sala
de emergencias?
Escriba aquí el número de teléfono para URGENCIAS
National Cancer Institute
Infecciones
(Available in English, Infection:
Managing Chemotherapy Side Effects)
Hable con su doctor o enfermera antes de tomar cualquier medicina.
Esto incluye la aspirina, el paracetamol, o el ibuprofeno.
Hable con su doctor o enfermera antes de cualquier inyección o
vacuna.
Llame a su doctor de inmediato
si tiene:
l Fiebre de 38° C o más alta.
Pregunte cuántas veces al día debe tomar su temperatura.
l Escalofríos
l Tos o irritación de garganta
l Dolor de oído
l Dolor de cabeza o en los senos de la cara
(senos nasales)
l Cuello tenso o adolorido
l Orina nublada o con sangre
l Dolor o ardor al orinar
l Sarpullido (“rash”)
l Llagas o una capa blanca en la boca o en
la lengua
l Hinchazón o enrojecimiento en cualquier
parte del cuerpo. Si usted tiene un catéter,
esté alerta si tiene hinchazón o dolor en
el área junto al catéter.
l Otro:
__________________________________
¿Tiene algún otro cambio o síntoma
que no parece normal? No espere. Llame de inmediato a su doctor o
enfermera.
“Necesito alejarme de gérmenes que
pudieran enfermarme. Me lavo las manos
muy bien antes de comer. Cuando no
puedo lavarme las manos con agua, uso un
desinfectante de manos”. —Ana Esperanza
Siga los siguientes consejos para
evitar las infecciones:
Lávese bien las manos.
l Siempre lávese las manos:
• antes de cocinar o comer
• después de ir al baño
• después de estar en un sitio público.
l Lávese bien las manos con agua y jabón. Pida a las
personas que le rodean que también se laven bien las
manos.
l Use desinfectante de manos (“hand sanitizer”)
cuando no puede encontrar agua ni jabón.
Practique la limpieza.
l Cepille sus dientes después de las comidas y antes de
acostarse. Use un cepillo de dientes muy suave (“soft
toothbrush”).
l Si tiene un catéter, mantenga el área limpia y seca
alrededor del mismo. Hable con su enfermera para
saber cómo cuidar esta área.
Evite los microbios.
l Aléjese de las personas que están enfermas o
resfriadas. Trate de mantenerse lejos de ellas si puede.
l Lave frutas, vegetales, y verduras crudas.
l Lávese las manos con cuidado después de tocar
carne cruda. Cocine bien la carne antes de comerla.
l Trate de mantenerse lejos de personas que hayan
sido vacunadas recientemente contra la varicela,
la polio y el sarampión.
l Si tiene mascotas, trate que otra persona limpie la
suciedad.
Trate de no cortarse la piel.
l Use una afeitadora eléctrica y no una navaja de afeitar.
l Límpiese bien y con cuidado después de ir al baño.
Diga a su doctor o enfermera si el área del recto (ano)
le duele o sangra.
l No se apriete los barros ni las espinillas.
Preguntas para su doctor o enfermera:
1. ¿Por cuáles problemas debo llamarles?
2. ¿Qué otros pasos debo seguir para evitar infecciones?
3. ¿Cómo y cuándo debo tomarme la temperatura?
4. ¿Por cuáles problemas debo ir de inmediato a la sala
de emergencias?
Escriba aquí el número de teléfono para URGENCIAS
Pérdida de apetito o anorexia del paciente oncológico. Consejos SEOM
PÉRDIDA DE APETITO O ANOREXIA
CONSEJOS PARA EL TRATAMIENTO DE LA PÉRDIDA
DE APETITO O ANOREXIA
• Tener en cuenta las preferencias del paciente.
• Variar la dieta, experimentar con recetas nuevas, sabores,
especias y diferentes tipos de comidas. Esto es muy importante,
ya que los gustos podrían variar cada día.
• Comer pequeñas cantidades de alimentos varias veces al día.
• Preparar los platos de forma variada y atractiva buscando
diferentes texturas y colores.
• Comenzar (antes de la dieta hipercalórica) con una dieta
normal, completa y de fácil digestión. De forma gradual,
y según se vaya tolerando, introducir en la dieta alimentos
de mayor valor nutritivo.
• Cuando se empiece a ganar peso, se pueden comer menos
ensaladas, verduras, productos desnatados que llenan
y tienen poco valor nutritivo.
• Evitar beber líquidos durante la comida. Beber al día de 2
a 3 litros de agua.
• Tomar una limonada, zumo de naranja, cóctel antes de
la comida si no está contraindicado (los frutos ácidos
pueden estimular el apetito).
• Si el médico lo permite, tomar un vasito de vino durante
la comida, puede estimular su apetito.
• Cocinar añadiendo al alimento proteínas y calorías
sin aumentar su volumen.
Algunas maneras son:
– Añadir miel, nata, leche en polvo o soja en polvo al alimento
que se está preparando.
– Añadir mantequilla, margarina, nata, crema de leche,
queso a la pasta italiana, arroz, patatas.
– Usar leche en vez de agua para diluir sopas condensadas
o purés.
– Añadir picada de frutos secos, huevo duro, tiras de jamón,
queso a las sopas, purés y cremas.
– Añadir crema de leche o leche en polvo a las salsas.
– Agregar una taza de leche en polvo a 1 litro de leche
entera.
– Añadir miel, caramelo líquido, frutos secos, leche condensada,
chocolate caliente o helado a los postres.
– Preferir los helados de turrón, avellana o coco a los helados
de fruta.
– Saltear las verduras con beicon, jamón, sofritos, salsas
como bechamel, mayonesa o salsa tártara.
– Usar la manteca de cacahuete con tostadas, galletas, etc.
– Utilizar soja en polvo para cocinar.
• Si tolera bien alguna comida, puede repetirla durante varios
días.
• Comer cuando se tenga apetito, aunque no sea en el horario
convencional.
• Intentar cambiar la rutina de comidas, por ejemplo, comer
en diferentes sitios.
• Servir la comida en un ambiente agradable y tranquilo.
• Propiciar compañía durante las comidas; cuando se coma
solo, escuchar la radio o ver la televisión. Hacer que las
comidas sean más agradables y relajantes e intentar salir
a comer fuera en alguna ocasión.
• Guardar el alimento cuando no se está comiendo.
• Caminar antes de las comidas puede estimular el apetito.
• Intentar comer algo antes de ir a la cama: no afectará a
su apetito para la siguiente comida.
• Usar platos grandes para que parezca que hay menos comida.
• Combinar en un solo plato un primero y un segundo.
• Si se toman dos platos, retirar el primer plato antes de
servir el segundo.
• Pedir a familiares o amigos que preparen la comida. Tener
comidas preparadas en la nevera y el congelador en
porciones individuales.
• Consultar al médico antes de usar suplementos nutricionales.
MENÚS RECOMENDADOS EN CASO DE ANOREXIA
Desayuno-merienda
• Tomar una cucharada de polen.
• Leche entera o semidescremada enriquecida con leche en
polvo.
• Leche de soja con vitaminas A, D y calcio.
• Leche de almendras.
• Café, café instantáneo o cacao.
• Bocadillos.
• Tostadas con queso fundido y nueces o mantequilla y mermelada
o mantequilla y salmón.
• Bollería.
• Galletas con membrillo y queso o mantequilla y cacao en
polvo.
• Yogur enriquecido con nata y cereales (copos de maíz,
muesli, etc.).
• Zumos enriquecidos.
Comida-cena
PRIMEROS PLATOS
• Ensalada de frutos secos con queso de cabra fundido.
• Ensalada de garbanzos o judías secas con picada de tomate,
pimiento y zanahoria.
• Verduras salteadas con jamón o beicon.
• Sopas enriquecidas con leche o soja.
• Sopas (de carne, pescado, vegetal) complementadas con
yema de huevo duro, arroz, jamón, sémola con piñones
tostados, rebanaditas de pan gratinadas con queso rallado
o garbanzos.
• Cremas de verduras o legumbres con levadura de cerveza
o sésamo tostado.
• Berenjenas rellenas de carne con queso gratinado.
• Pastas italianas con salsa bechamel ligera.
• Patatas al horno con queso fundido.
SEGUNDOS PLATOS
• Bistec de ternera con setas de guarnición.
• Escalope de pollo a la plancha con verduritas.
• Conejo en salsa suave.
• Mero al horno con guisantes y champiñones.
• Trucha con piñones o con almendras.
• Bacalao con tomate.
• Huevos revueltos con jamón y setas.
• Tortilla de patatas, de queso, etc.
POSTRES
• Fruta en almíbar con nata o leche condensada.
• Batido de «petit suisse» y yogur.
• Uvas, higos, plátanos.
• Flan o natillas caseras, arroz con leche, helados de frutos
secos, leche con fresas, zumo de naranja y helado de
vainilla, leche con helado y frutas y caramelo.
RECETAS ACONSEJADAS PARA PACIENTES
CON ANOREXIA
SANGRÍA DE CÍTRICOS
Antes de la comida puede tomar un zumo, cóctel o una sangría
de cítricos para abrir el apetito.
Ingredientes: 1 lima, 1 limón, 1 naranja, 1 litro de zumo de
uva blanca, 1/2 de sifón, hielo picado.
Preparación: Corte la lima, el limón y la naranja en dos.
Exprima el zumo de una de cada dos mitades y corte las
restantes en rodajas finas. En una jarra, mezcle el zumo
de uva, el sifón y el zumo y las rodajas de lima, limón y
naranja. Llene una copa con hielo picado hasta 1/4 de su
capacidad; vierta la sangría y ponga una rodaja de fruta en
cada copa.
PATATAS AL HORNO CON QUESO FUNDIDO
Ingredientes: 2 patatas grandes, 1/2 cebolla picada, 1 cucharada
de harina, sal y pimienta, 1 vaso de leche al que
podemos añadir una cucharada de leche en polvo, 2 cucharadas
de queso rallado.
Preparación: En una fuente de horno, forme una capa con
patatas a rodajas; espolvoréelas con la mitad de la cebolla
y luego con la mitad de harina. Sazone con sal y pimienta al
gusto. Haga otra capa igual. Vierta la leche caliente por encima.
Espolvoree con el queso. Meta la fuente en el horno
a 180 oC durante 45 minutos o hasta que las patatas estén
tiernas.
CREMA DE ALUBIAS
Ingredientes: 50 gramos de alubias, 1 vaso de leche al que
podemos añadir una cucharada de leche en polvo, un bol pequeño
de salsa bechamel, 1 cucharadita de mantequilla, sal
y pimienta.
Preparación: Ponga las alubias en remojo durante varias horas.
Hiérvalas en agua con sal. Cuando estén cocidas, páselas
por la batidora. Ponga el puré de alubias en una cazuela
junto con la salsa bechamel. Sazónelo con sal y pimienta. Añada
la leche y vaya removiendo la mezcla hasta obtener la consistencia
cremosa que desee. En el momento de servir el
puré, póngale la mantequilla para que se derrita.
ENSALADA DE PLÁTANO CON MANTECA
DE CACAHUETE
Ingredientes: 1 plátano, 2 endibias, 30 gramos de manteca
de cacahuete, 1 yogur, 1 cucharadita de zumo de limón.
Preparación: Pase el yogur, el zumo de limón y la manteca
de cacahuete por la batidora. Pele el plátano, córtelo a rodajas
y póngalo sobre las hojas de las endibias. Cúbralo con
la mezcla anterior.
ENSALADA DE INVIERNO
Ingredientes: 1 nabo, hojas de escarola troceada, 1 zanahoria,
1/2 manzana, 2 cucharadas de pasas, nueces, 1 yogur
natural enriquecido con nata, 1 cucharadita de zumo de
limón.
Preparación: Ralle el nabo, la zanahoria, la manzana y póngalos
con la escarola troceada. Mezcle todo con el yogur y
el zumo de limón. Muela los frutos secos y espolvoréelos
por encima.
BRÓCOLI CON BECHAMEL
Ingredientes: 1/2 kilo de brócolis, 1 huevo, mantequilla, leche,
aceite de oliva virgen, sal y pimienta.
Preparación: Despoje los brócolis de sus troncos gordos
y las hojas exteriores. Póngalos en una olla al vapor durante
20 minutos. Mientras, prepare un vaso de bechamel,
añadiendo pimienta al final. Cueza el huevo hasta
que esté bien duro y pélelo. Unte de aceite una fuente refractaria
y coloque los brócolis, cubriéndolos con la bechamel.
Adorne con el huevo a rodajas y póngalo al horno
y gratine 5 minutos.
ESPAGUETIS CON FRUTOS SECOS
Ingredientes: 100 gramos de espaguetis, nueces peladas,
6 avellanas peladas, 1 cucharada de piñones, 1 cucharadita
de mantequilla, sal, aceite de oliva virgen, 1 cucharada
de queso parmesano rallado, pimienta y 5 cucharadas
de crema de leche.
Preparación: Ponga sal y una cucharada de aceite en una
olla alta con abundante agua. Cuando esté hirviendo, ponga
los espaguetis durante unos 5 minutos hasta que estén
al dente. En un mortero,machaque los piñones, las
nueces y las avellanas hasta reducir a polvo los frutos secos.
Mézclelos con 1 cucharadita de mantequilla, unas 5
cucharadas de crema de leche y una pizca de pimienta
hasta conseguir una pasta uniforme. Cuando estén los
espaguetis al dente, escúrralos bien y échelos en una
fuente. Añada la pasta de frutos secos, revuelva con cucharas
de madera, rocíe la fuente con queso rallado, y ya
están listos para servir.
TRUCHA CON SALSA DE ALMENDRA
Ingredientes: una trucha mediana, 10 almendras crudas,
1/2 limón, 1/2 diente de ajo, aceite de oliva virgen, sal
y 1 cucharada de perejil picado.
Preparación: Limpie y lave la trucha, póngale sal, rebócela
en harina y fríala en una sartén con poco aceite. Después,póngala en una fuente refractaria al calor. Mientras,en el mismo aceite ponga el ajo y las almendras para dorarlos.
En un mortero ponga el ajo, las almendras, 2 cucharadas
de aceite (del que se utilizó con la trucha), macháquelo todo muy bien añadiendo
el perejil picado y el zumo del medio limón. Vierta esta salsa sobre la trucha y
ponga la fuente al horno para que dé el último hervor, sólo 2 o 3 minutos.
BONIATOS CON CANELA
Ingredientes: 1 boniato mediano, 1 cucharada de canela
en polvo, 1 cucharada de
azúcar.
Preparación: Lave el boniato
y póngalo al vapor sin pelar.
La cocción es de unos 30 minutos,pero para asegurarse que está en su punto, pínchelo
con un cuchillo. Si está tierno, retírelo. Cuando se haya enfriado, pélelo y córtelo
en varios trozos de forma alargada. En un plato ponga un trozo al lado del otro y espolvorée la canela y el azúcar. Están mejor si se comen un poco fríos, póngalos en la nevera.
LECHE CON FRESAS
Ingredientes: 250 gramos de fresas, 1 litro de leche, 6 cucharadas
soperas de azúcar y 150 gramos de nata.
Preparación: Triture las fresas y páselas por el colador chino.
Este puré mézclelo con la leche bien fría y añada 4 cucharadas
de azúcar, removiendo bien hasta que quede una
pasta lisa. Viértala en los vasos y eche por encima nata,
que antes habrá mezclado con las 2 cucharadas de azúcar.
ZUMOS
Los zumos pueden diluirse con agua. Es recomendable licuar
cada fruta o verdura por separado y mezclar los diferentes
zumos poco a poco.
ZUMOS RICOS EN HIERRO Y ÁCIDO FÓLICO
Ingredientes: 1/2 remolacha, 50 gramos de col rizada y 2 zanahorias
grandes.
Ingredientes: 175 gramos de fresas, 50 gramos de moras
y 1 manzana.
ZUMOS MÁS ENERGÉTICOS
Ingredientes: 1 mango, 1/2 piña, un plátano aplastado con
un tenedor, 1/2 vaso de leche o un yogur natural, 1 cucharadita
de coco desecado, 1/2 cucharadita de miel y 1 cucharadita
de germen de trigo.
Ingredientes: 250 gramos de fresas, 10 frambuesas, 3 albaricoques,
1/2 vaso de leche o de yogur, 1/2 cucharadita de miel y 1 cucharadita de germen
de trigo.
ZUMOS DE REFUERZO MULTIMINERAL
Ingredientes: 1 pimiento rojo, 6 hojas de lechuga y 1 zanahoria
grande.
Ingredientes: 3 tomates, 1 manojo de perejil, 1/2 nabo.
ZUMOS DE REFUERZO MULTIVITAMÍNICO
Ingredientes: Un pequeño racimo de uvas, 1 nectarina.
Ingredientes: 2 kiwis, 1 pera y 2 albaricoques.
CONSEJOS PARA EL TRATAMIENTO DE LA PÉRDIDA
DE APETITO O ANOREXIA
• Tener en cuenta las preferencias del paciente.
• Variar la dieta, experimentar con recetas nuevas, sabores,
especias y diferentes tipos de comidas. Esto es muy importante,
ya que los gustos podrían variar cada día.
• Comer pequeñas cantidades de alimentos varias veces al día.
• Preparar los platos de forma variada y atractiva buscando
diferentes texturas y colores.
• Comenzar (antes de la dieta hipercalórica) con una dieta
normal, completa y de fácil digestión. De forma gradual,
y según se vaya tolerando, introducir en la dieta alimentos
de mayor valor nutritivo.
• Cuando se empiece a ganar peso, se pueden comer menos
ensaladas, verduras, productos desnatados que llenan
y tienen poco valor nutritivo.
• Evitar beber líquidos durante la comida. Beber al día de 2
a 3 litros de agua.
• Tomar una limonada, zumo de naranja, cóctel antes de
la comida si no está contraindicado (los frutos ácidos
pueden estimular el apetito).
• Si el médico lo permite, tomar un vasito de vino durante
la comida, puede estimular su apetito.
• Cocinar añadiendo al alimento proteínas y calorías
sin aumentar su volumen.
Algunas maneras son:
– Añadir miel, nata, leche en polvo o soja en polvo al alimento
que se está preparando.
– Añadir mantequilla, margarina, nata, crema de leche,
queso a la pasta italiana, arroz, patatas.
– Usar leche en vez de agua para diluir sopas condensadas
o purés.
– Añadir picada de frutos secos, huevo duro, tiras de jamón,
queso a las sopas, purés y cremas.
– Añadir crema de leche o leche en polvo a las salsas.
– Agregar una taza de leche en polvo a 1 litro de leche
entera.
– Añadir miel, caramelo líquido, frutos secos, leche condensada,
chocolate caliente o helado a los postres.
– Preferir los helados de turrón, avellana o coco a los helados
de fruta.
– Saltear las verduras con beicon, jamón, sofritos, salsas
como bechamel, mayonesa o salsa tártara.
– Usar la manteca de cacahuete con tostadas, galletas, etc.
– Utilizar soja en polvo para cocinar.
• Si tolera bien alguna comida, puede repetirla durante varios
días.
• Comer cuando se tenga apetito, aunque no sea en el horario
convencional.
• Intentar cambiar la rutina de comidas, por ejemplo, comer
en diferentes sitios.
• Servir la comida en un ambiente agradable y tranquilo.
• Propiciar compañía durante las comidas; cuando se coma
solo, escuchar la radio o ver la televisión. Hacer que las
comidas sean más agradables y relajantes e intentar salir
a comer fuera en alguna ocasión.
• Guardar el alimento cuando no se está comiendo.
• Caminar antes de las comidas puede estimular el apetito.
• Intentar comer algo antes de ir a la cama: no afectará a
su apetito para la siguiente comida.
• Usar platos grandes para que parezca que hay menos comida.
• Combinar en un solo plato un primero y un segundo.
• Si se toman dos platos, retirar el primer plato antes de
servir el segundo.
• Pedir a familiares o amigos que preparen la comida. Tener
comidas preparadas en la nevera y el congelador en
porciones individuales.
• Consultar al médico antes de usar suplementos nutricionales.
MENÚS RECOMENDADOS EN CASO DE ANOREXIA
Desayuno-merienda
• Tomar una cucharada de polen.
• Leche entera o semidescremada enriquecida con leche en
polvo.
• Leche de soja con vitaminas A, D y calcio.
• Leche de almendras.
• Café, café instantáneo o cacao.
• Bocadillos.
• Tostadas con queso fundido y nueces o mantequilla y mermelada
o mantequilla y salmón.
• Bollería.
• Galletas con membrillo y queso o mantequilla y cacao en
polvo.
• Yogur enriquecido con nata y cereales (copos de maíz,
muesli, etc.).
• Zumos enriquecidos.
Comida-cena
PRIMEROS PLATOS
• Ensalada de frutos secos con queso de cabra fundido.
• Ensalada de garbanzos o judías secas con picada de tomate,
pimiento y zanahoria.
• Verduras salteadas con jamón o beicon.
• Sopas enriquecidas con leche o soja.
• Sopas (de carne, pescado, vegetal) complementadas con
yema de huevo duro, arroz, jamón, sémola con piñones
tostados, rebanaditas de pan gratinadas con queso rallado
o garbanzos.
• Cremas de verduras o legumbres con levadura de cerveza
o sésamo tostado.
• Berenjenas rellenas de carne con queso gratinado.
• Pastas italianas con salsa bechamel ligera.
• Patatas al horno con queso fundido.
SEGUNDOS PLATOS
• Bistec de ternera con setas de guarnición.
• Escalope de pollo a la plancha con verduritas.
• Conejo en salsa suave.
• Mero al horno con guisantes y champiñones.
• Trucha con piñones o con almendras.
• Bacalao con tomate.
• Huevos revueltos con jamón y setas.
• Tortilla de patatas, de queso, etc.
POSTRES
• Fruta en almíbar con nata o leche condensada.
• Batido de «petit suisse» y yogur.
• Uvas, higos, plátanos.
• Flan o natillas caseras, arroz con leche, helados de frutos
secos, leche con fresas, zumo de naranja y helado de
vainilla, leche con helado y frutas y caramelo.
RECETAS ACONSEJADAS PARA PACIENTES
CON ANOREXIA
SANGRÍA DE CÍTRICOS
Antes de la comida puede tomar un zumo, cóctel o una sangría
de cítricos para abrir el apetito.
Ingredientes: 1 lima, 1 limón, 1 naranja, 1 litro de zumo de
uva blanca, 1/2 de sifón, hielo picado.
Preparación: Corte la lima, el limón y la naranja en dos.
Exprima el zumo de una de cada dos mitades y corte las
restantes en rodajas finas. En una jarra, mezcle el zumo
de uva, el sifón y el zumo y las rodajas de lima, limón y
naranja. Llene una copa con hielo picado hasta 1/4 de su
capacidad; vierta la sangría y ponga una rodaja de fruta en
cada copa.
PATATAS AL HORNO CON QUESO FUNDIDO
Ingredientes: 2 patatas grandes, 1/2 cebolla picada, 1 cucharada
de harina, sal y pimienta, 1 vaso de leche al que
podemos añadir una cucharada de leche en polvo, 2 cucharadas
de queso rallado.
Preparación: En una fuente de horno, forme una capa con
patatas a rodajas; espolvoréelas con la mitad de la cebolla
y luego con la mitad de harina. Sazone con sal y pimienta al
gusto. Haga otra capa igual. Vierta la leche caliente por encima.
Espolvoree con el queso. Meta la fuente en el horno
a 180 oC durante 45 minutos o hasta que las patatas estén
tiernas.
CREMA DE ALUBIAS
Ingredientes: 50 gramos de alubias, 1 vaso de leche al que
podemos añadir una cucharada de leche en polvo, un bol pequeño
de salsa bechamel, 1 cucharadita de mantequilla, sal
y pimienta.
Preparación: Ponga las alubias en remojo durante varias horas.
Hiérvalas en agua con sal. Cuando estén cocidas, páselas
por la batidora. Ponga el puré de alubias en una cazuela
junto con la salsa bechamel. Sazónelo con sal y pimienta. Añada
la leche y vaya removiendo la mezcla hasta obtener la consistencia
cremosa que desee. En el momento de servir el
puré, póngale la mantequilla para que se derrita.
ENSALADA DE PLÁTANO CON MANTECA
DE CACAHUETE
Ingredientes: 1 plátano, 2 endibias, 30 gramos de manteca
de cacahuete, 1 yogur, 1 cucharadita de zumo de limón.
Preparación: Pase el yogur, el zumo de limón y la manteca
de cacahuete por la batidora. Pele el plátano, córtelo a rodajas
y póngalo sobre las hojas de las endibias. Cúbralo con
la mezcla anterior.
ENSALADA DE INVIERNO
Ingredientes: 1 nabo, hojas de escarola troceada, 1 zanahoria,
1/2 manzana, 2 cucharadas de pasas, nueces, 1 yogur
natural enriquecido con nata, 1 cucharadita de zumo de
limón.
Preparación: Ralle el nabo, la zanahoria, la manzana y póngalos
con la escarola troceada. Mezcle todo con el yogur y
el zumo de limón. Muela los frutos secos y espolvoréelos
por encima.
BRÓCOLI CON BECHAMEL
Ingredientes: 1/2 kilo de brócolis, 1 huevo, mantequilla, leche,
aceite de oliva virgen, sal y pimienta.
Preparación: Despoje los brócolis de sus troncos gordos
y las hojas exteriores. Póngalos en una olla al vapor durante
20 minutos. Mientras, prepare un vaso de bechamel,
añadiendo pimienta al final. Cueza el huevo hasta
que esté bien duro y pélelo. Unte de aceite una fuente refractaria
y coloque los brócolis, cubriéndolos con la bechamel.
Adorne con el huevo a rodajas y póngalo al horno
y gratine 5 minutos.
ESPAGUETIS CON FRUTOS SECOS
Ingredientes: 100 gramos de espaguetis, nueces peladas,
6 avellanas peladas, 1 cucharada de piñones, 1 cucharadita
de mantequilla, sal, aceite de oliva virgen, 1 cucharada
de queso parmesano rallado, pimienta y 5 cucharadas
de crema de leche.
Preparación: Ponga sal y una cucharada de aceite en una
olla alta con abundante agua. Cuando esté hirviendo, ponga
los espaguetis durante unos 5 minutos hasta que estén
al dente. En un mortero,machaque los piñones, las
nueces y las avellanas hasta reducir a polvo los frutos secos.
Mézclelos con 1 cucharadita de mantequilla, unas 5
cucharadas de crema de leche y una pizca de pimienta
hasta conseguir una pasta uniforme. Cuando estén los
espaguetis al dente, escúrralos bien y échelos en una
fuente. Añada la pasta de frutos secos, revuelva con cucharas
de madera, rocíe la fuente con queso rallado, y ya
están listos para servir.
TRUCHA CON SALSA DE ALMENDRA
Ingredientes: una trucha mediana, 10 almendras crudas,
1/2 limón, 1/2 diente de ajo, aceite de oliva virgen, sal
y 1 cucharada de perejil picado.
Preparación: Limpie y lave la trucha, póngale sal, rebócela
en harina y fríala en una sartén con poco aceite. Después,póngala en una fuente refractaria al calor. Mientras,en el mismo aceite ponga el ajo y las almendras para dorarlos.
En un mortero ponga el ajo, las almendras, 2 cucharadas
de aceite (del que se utilizó con la trucha), macháquelo todo muy bien añadiendo
el perejil picado y el zumo del medio limón. Vierta esta salsa sobre la trucha y
ponga la fuente al horno para que dé el último hervor, sólo 2 o 3 minutos.
BONIATOS CON CANELA
Ingredientes: 1 boniato mediano, 1 cucharada de canela
en polvo, 1 cucharada de
azúcar.
Preparación: Lave el boniato
y póngalo al vapor sin pelar.
La cocción es de unos 30 minutos,pero para asegurarse que está en su punto, pínchelo
con un cuchillo. Si está tierno, retírelo. Cuando se haya enfriado, pélelo y córtelo
en varios trozos de forma alargada. En un plato ponga un trozo al lado del otro y espolvorée la canela y el azúcar. Están mejor si se comen un poco fríos, póngalos en la nevera.
LECHE CON FRESAS
Ingredientes: 250 gramos de fresas, 1 litro de leche, 6 cucharadas
soperas de azúcar y 150 gramos de nata.
Preparación: Triture las fresas y páselas por el colador chino.
Este puré mézclelo con la leche bien fría y añada 4 cucharadas
de azúcar, removiendo bien hasta que quede una
pasta lisa. Viértala en los vasos y eche por encima nata,
que antes habrá mezclado con las 2 cucharadas de azúcar.
ZUMOS
Los zumos pueden diluirse con agua. Es recomendable licuar
cada fruta o verdura por separado y mezclar los diferentes
zumos poco a poco.
ZUMOS RICOS EN HIERRO Y ÁCIDO FÓLICO
Ingredientes: 1/2 remolacha, 50 gramos de col rizada y 2 zanahorias
grandes.
Ingredientes: 175 gramos de fresas, 50 gramos de moras
y 1 manzana.
ZUMOS MÁS ENERGÉTICOS
Ingredientes: 1 mango, 1/2 piña, un plátano aplastado con
un tenedor, 1/2 vaso de leche o un yogur natural, 1 cucharadita
de coco desecado, 1/2 cucharadita de miel y 1 cucharadita
de germen de trigo.
Ingredientes: 250 gramos de fresas, 10 frambuesas, 3 albaricoques,
1/2 vaso de leche o de yogur, 1/2 cucharadita de miel y 1 cucharadita de germen
de trigo.
ZUMOS DE REFUERZO MULTIMINERAL
Ingredientes: 1 pimiento rojo, 6 hojas de lechuga y 1 zanahoria
grande.
Ingredientes: 3 tomates, 1 manojo de perejil, 1/2 nabo.
ZUMOS DE REFUERZO MULTIVITAMÍNICO
Ingredientes: Un pequeño racimo de uvas, 1 nectarina.
Ingredientes: 2 kiwis, 1 pera y 2 albaricoques.
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