Leucovorin (LV) is an intravenously administered derivative of the vitamin, folic acid. The administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists, such as methotrexate. However, leucovorin can also be used to enhance the effects of 5-FU. Leucovorin is metabolized in the body to a compound that stabilizes the binding of 5-FU to thymidylate synthase. This enhances the inhibition of thymidylate synthase by 5-FU. Combined data from numerous trials indicate a two-fold increase in tumor response rates with 5-FU plus leucovorin compared with 5-FU alone (23% vs 12%), plus a small increase in survival.