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[The biochemical modulation of 5-fluorouracil by leucovorin].

5-fluorouracil (5-FU) is the most effective drug in the treatment of advanced colorectal carcinoma and has definite activity in a variety of other solid tumors. However, remissions occur in only about 20% of the patients and usually are of short duration. Biochemical modulation is a way of enhancing the efficacy of 5-FU by manipulation of intracellular metabolic pathways. Leucovorin (LV) prolongs the inhibition of the key enzyme, thymidylate synthetase, by stabilizing the ternary complex with activated 5-FU, thus leading to "thymidine-less" death. Phase II trials showed promising response rates in colorectal, gastric, and breast cancer. This translated into prolonged survival and into an increased therapeutic index in some phase III studies comparing the combination 5-FU/LV with 5-FU monotherapy in colorectal cancer. The present article focuses on the pharmacological background of the therapy with 5-FU/LV, summarizes the clinical data and gives a short overview on other ways of increasing the therapeutic index of 5-FU.