Cough in Patients With Lung Cancer

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Aprepitant Decreases Cough in Patients With Lung Cancer

Kate O'Rourke
October 13, 2015


BOSTON — Aprepitant (Emend, Merck & Co, Inc), a drug approved for chemotherapy-induced nausea and vomiting, has shown promise as an antitussive agent in a small trial of patients with lung cancer. This is the first trial to assess the use of a centrally acting neurokinin-1 (NK-1) receptor antagonist as an antitussive agent, the researchers noted.

"Aprepitant led to a significant reduction in cough frequency," said lead study author Amelie Harle, MD, PhD, Christie Hospital NHS Foundation Trust and the University of Manchester, United Kingdom.

Cough is a complex symptom that can have a significant impact on a patient's quality of life, she explained. Cough can be very severe in lung cancer patients. "The neuronal pathways involved in controlling cough are complex. Neurokinins are important mediators of cough in the central nervous system across five different species of animal," said Dr Harle. "For that reason, we thought it was an important target to effect in humans."

In the new study, presented at the recent Palliative Care in Oncology (PCOS) Symposium 2015, researchers enrolled lung cancer patients who had a bothersome cough in an exploratory single-arm, double-blind, placebo-controlled crossover trial. Patients received either aprepitant, 125 mg on day 1 and 80 mg on days 2 and 3, or matched placebo capsules. After a 3-day washout period, patients crossed over to placebo or aprepitant for 3 days (days 7-9).

For a 24-hour period prior to receiving drug or placebo and during the trial, patients wore a monitoring machine during the day that recorded the number of coughs per hour. The FDA-approved machine hangs around the patient's waist, similar to a fanny pack; a miniature microphone on the individual's lapel allows for ambulatory monitoring of cough. Patients also completed validated subjective tools, including the Manchester Cough in Lung Cancer Scale, the Visual Analogue Scale, the European Organization for Research and Treatment of Cancer QLQ-C30, and the Common Terminology Criteria for Adverse Events v4.0.

Daytime cough frequency was 15.9 coughs per hour at baseline, 16.2 coughs per hour in patients receiving placebo, and 12.8 coughs per hour in patients receiving aprepitant (P = .03). Aprepitant also improved outcomes on subjective cough tools. "The effect was modest, but, interestingly, when we looked at the subjective measures, patients were able to report that difference in all four measures," Dr Harle said.

Adverse events were minimal, she added.

Table. Select Subjective Outcomes in Lung Cancer Patients
Outcome Baseline Placebo Aprepitant P -value
Manchester Cough in Lung Cancer Scale (range 1 - 50, with a high score representing worse cough impact) 25.2 21.7 19.5 0.001
Visual Analogue Scale (high score represents worse severity) 57.0 mm 49.8 mm 40.8 mm 0.008



"This is the first antitussive trial in lung cancer patients using the objective quantification of cough," said Dr Harke. "Further evaluation of NK-1 inhibitors is warranted in this population. It may be that the NK-1 pathway may be a key component of cough mechanisms in lung cancer. We hope that these data will inform the design of a definitive trial in the future."

Here we have people studying things that upset the patient. They are not studying just the tumor. Dr Dorothy Keefe


According to Dorothy Keefe, MD, an oncologist at Royal Adelaide Hospital in South Australia, who served as the study discussant at the meeting, cough is a huge problem for many patients, and the "elegant" study demonstrates patient-centered care. "Here we have people studying things that upset the patient. They are not studying just the tumor," said Dr Keefe. "This is a fascinating study because it takes the known mechanism of cough and matches it with the known mechanism of action of an antinausea medication that we are already using. This is a really nice proof of concept. It's a small sample, but you have to start somewhere. It's a sound basis for future investigation."

Dr Keefe and Dr Harle have disclosed no relevant financial relationships.

Palliative Care in Oncology Symposium (PCOS) 2015: Abstract 2. Presented October 10, 2015.