Metronomic Methotrexate Regimen Proposed For Platinum-Refractory Oral Cancer

Metronomic Methotrexate Regimen Proposed For Platinum-Refractory Oral Cancer
Patients with treatment-refractory squamous cell carcinoma of the oral cavity may respond to a metronomic schedule of oral methotrexate, erlotinib and celecoxib
Date: 25 Sep 2019
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Head and Neck Cancers / Anticancer Agents
medwireNews: Phase I/II trial results suggest that an oral metronomic regimen of methotrexate, erlotinib and celecoxib may have activity against platinum-refractory squamous cell cancer of the oral cavity.

The researchers describe their findings as “exciting” when compared against historical response rates of up to 13.6% and progression-free survival (PFS) of up to 2.3 months for cytotoxic chemotherapy agents and nivolumab.

The optimal biological dose of methotrexate 9 mg/m2 per week was identified in phase I and this was given once per week alongside erlotinib 150 mg/day and celecoxib 200 mg twice daily to 76 patients in phase II.

The participants had all progressed within 1 month of surgery or radiation, or within 6 months of receiving platinum-based systemic treatment, explain Kumar Prabhash and colleagues, from the Tata Memorial Centre in Mumbai, India.

After a median follow-up of 6.8 months, the median PFS was 4.6 months, with 3- and 6-month PFS rates of 71.1% and 34.5%, respectively. And at data cutoff, the median overall survival (OS) duration was 7.2 months with a 6-month rate of 61.2%.

At 2 months, 37.4% of patients achieved a response to treatment and this increased to 42.9% over follow-up. The median response durations in these two groups were 2.1 and 4.4 months, respectively.

Safety analysis of 88 patients indicated the most common adverse events were fatigue (85.2%), rash (80.7%) and anaemia (80.7%), while other less common events included grade 3–4 hyponatremia (14.8%) and elevated alanine transaminase (5.7%). Overall, 13.6% of patients required a dose reduction, most commonly for the methotrexate treatment (11.4%).

“In conclusion, the combination of erlotinib, [methotrexate], and celecoxib in platinum-insensitive oral cancer results in promising [response rates], PFS, and OS”, Kumar Prabhash and co-authors conclude in the Journal of Clinical Oncology.

And they recommend that “[i]ts activity needs to be confirmed in a phase III randomized study.”



Reference

Patil VM, Noronha V, Joshi A, et al. Phase I/II study of palliative triple metronomic chemotherapy in platinum-refractory/early-failure oral cancer . J Clin Oncol; Advance online publication 20 September 2019. DOI: 10.1200/JCO.19.01076