Folate during antifolate chemotherapy: what we know... and do not know.

The nutrient folate is essential for normal cell growth and development. Enzymes that require folate as a cofactor have been common targets for chemotherapeutic agents. Limited clinical guidance is available regarding optimal levels of dietary or supplemental folate intake during antifolate chemotherapy to meet the goals of minimizing treatment-related toxicity yet preserving treatment effectiveness. Patients with higher folate intake may experience less treatment-related toxicities; however, the concern is that folate may interfere with the effectiveness of the antifolate treatment and possibly support tumor growth. This article will review folate and antifolate metabolism and review the current body of knowledge regarding the interactions between folates and antifolates. Future research in this area should include evaluation of pretreatment folate status and dietary and supplemental folate intake before, during, and after treatment.