Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer.

Background: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials.

Patients And Methods: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an anti-epidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent.