ENHANCED INHIBITION OF THYMIDYLATE SYNTHASE BY 5-FLUOROURACIL AND [6S]LEUCOVORIN COMBINATION THERAPY FOR BREAST-CANCER

The influence of the addition of [6S] leucovorin (LV) to 5-fluorouracil (5-FU) preoperative chemotherapy was examined in patients with surgically resectable breast cancer who had had no prior treatment. The patients underwent one of the following three treatments at their will: (1) 5-FU 500 mg/m(2) administered by an IV bolus; (2) [6S]LV 250 mg/m(2) infused intravenously over two hours, with 5-FU 500 mg/m(2) as an IV bolus at the midpoint of [6S]LV infusion, (3) no drug treatment. Tumors were resected 24 hours after the dose of 5-FU with or without [6S]LV. These studies confirmed an increased stabilization of 5-fluorodeoxyuridine monophosphate (FdUMP)-thymidylate synthase(TS)-folate ternary complex with the addition of [6S]LV. An increase of total TS activity was also found.