Synopsis

Source of validity: Scientific
Rating (out of 5): 5

Leucovorin (also known as folinic acid) is scientifically validated for use in chemotherapy support, particularly with methotrexate and 5-fluorouracil (5-FU) regimens. Its primary role is as a "rescue" agent following high-dose methotrexate therapy. Methotrexate inhibits dihydrofolate reductase, blocking folate metabolism and DNA synthesis, which is effective against cancer cells but also toxic to normal rapidly dividing cells such as those in the bone marrow and gastrointestinal tract. Leucovorin bypasses the methotrexate-induced block in folate metabolism, selectively "rescuing" normal cells while maintaining the antitumor effect, as cancer cells are less efficient at utilizing leucovorin. This use is well-established and supported by extensive clinical evidence and guideline recommendations (e.g., by the National Comprehensive Cancer Network and the World Health Organization). Additionally, leucovorin is used to enhance the effect of 5-FU in colorectal cancer. When combined, leucovorin stabilizes the binding of 5-FU to its target enzyme (thymidylate synthase), increasing cytotoxicity against tumor cells. This synergistic effect is also supported by randomized controlled trials and meta-analyses. In summary, leucovorin's use in chemotherapy is underpinned by robust scientific evidence, both for reducing toxicity with methotrexate and enhancing efficacy with 5-FU, making its use standard in clinical oncology practice.

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