metformin + 5-fluorouracil + leucovorin

This investigational combination therapy consists of the biguanide metformin, the antimetabolite 5-fluorouracil (5-FU), and the folate analogue leucovorin. Developed and studied by the Instituto do Câncer do Estado de São Paulo (ICESP), this regimen is being evaluated for the treatment of refractory metastatic colorectal cancer (mCRC). Metformin, traditionally used for type 2 diabetes, is hypothesized to exert antitumor effects by activating adenosine monophosphate-activated protein kinase (AMPK), which leads to the inhibition of the mammalian target of rapamycin (mTOR) pathway and a reduction in systemic insulin levels. 5-fluorouracil acts by inhibiting thymidylate synthase to disrupt DNA synthesis, while leucovorin is administered to stabilize the binding of 5-FU to its target, thereby enhancing its cytotoxic efficacy. A Phase 2 trial investigated this combination in patients who had progressed on standard therapies including oxaliplatin and irinotecan.

Other names

Metformin and FluorouracilMetformin + 5-FU + Leucovorin