fluorouracil + levofolinic acid + methotrexate

This is a combination regimen of three drugs—fluorouracil (5-FU), levofolinic acid (the active enantiomer of folinic acid, also known as leucovorin or calcium folinate), and methotrexate—used in the treatment of advanced cancers, particularly those of the digestive tract such as colorectal, gastric, and biliary tract cancers. - **Fluorouracil** is an antimetabolite that inhibits thymidylate synthase, disrupting DNA synthesis and leading to cell death. - **Levofolinic acid** enhances the cytotoxic effect of fluorouracil by stabilizing its binding to thymidylate synthase; it also serves as a "rescue" agent to reduce toxicity from high-dose methotrexate by bypassing dihydrofolate reductase inhibition. - **Methotrexate** is a folic acid antagonist that inhibits dihydrofolate reductase, blocking DNA synthesis in rapidly dividing cells. In this regimen, it acts both directly against tumor cells and biochemically modulates the activity of fluorouracil when given sequentially with levofolinic acid[6][4][2]. The combination aims for double biochemical modulation—methotrexate primes tumor cells for increased sensitivity to subsequent 5-FU plus levofolinic acid administration[6]. This approach has shown clinical activity in advanced digestive tract malignancies with manageable toxicity.

Other names

5-fluorouracil + levofolinic acid + methotrexate5-FU + LFA + MTX