Cancer: Effect of metformin in combination with cisplatin and radiotherapy to treat locally advanced head and neck squamous cell carcinoma.

The 5-year total survival rate (OS) for patients with locallate head and neck squamous cell carcinoma (LAHNSCC) is still 50%, emphasizing the need for improved treatment.
in retrospective studies found that an anti-diabetic drug metformin could improve the survival of HNSCC patients.
therefore, the purpose of this study is to conduct a phase 1 study to explore the efficacy of metformin combined with chemical radiotherapy in patients with LAHNSCC.
patients with non-diabetic LAHNSCC were given an upgraded dose of metformin and CRT.
metformin queue doses include 2000 mg, 2550 mg and 3000 mg per day, in addition to cisplatin (100 mg/m2 for the first, 22and 43 days) and standard radiotherapy (70 g).
adverse events are classified according to the U.S. National Cancer Institute's Common Terminology Standard for Adverse Events (version 4.03). a total of 20 patients were enrolled in the
, two of whom withdrew their consent. the median age of
patients was 56 years, mostly male (83%), white (88%), p16 positive (72%) and smoker (61%). the median exposure time of
metformin was 28.5 days. the most common level3 toxicity in
was nausea (11%), vomiting (11%), mucositis (6%), acute kidney injury (17%), anemia (6%) and white blood cell reduction (11%).
dose-restrictive toxicity includes diarrhea and acute kidney injury.
after 19 months of median follow-up, the total survival rate and the non-progression survival rate of 2 years were 90% and 84%, respectively.
no hypoglycemia events or lactic acidosis were observed.
cisplatin administration does not seem to affect the pharmacokinetics of metformin.
The maximum tolerable dose of metformin could not be determined given the limited number of patients who were resistant to metformin during chemotherapy.
in general, this study is the first phase 1 trial that combines metformin with chemotherapy.
In this limited patient population, the overall survival rate and the non-progression survival rate are encouraging and need to be further explored in Phase 2 trials.
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