A phase I trial of protracted 5-fluorouracil infusion and oral calcium leucovorin.

This phase I study of 36 patients was performed to identify the maximal tolerated dose of oral calcium leucovorin (CLV) that could be concomitantly administered with protracted 5-fluorouracil (5-FU) infusion (greater than 30 days). Administration of CLV in very small doses (5 mg p.o. q8h) with 5-FU, 200-300 mg/m2/day, resulted in excessive toxicity requiring treatment interruption in all patients. Subsequent reduction in the dose of 5-FU to 100 mg/m2/day with simultaneous administration of CLV, 5 mg p.o. q8h, decreased the toxicity and allowed for protracted administration of the combination. In subsequent patients the dose of oral CLV was increased to 22.5 mg p.o. q8h, which resulted in treatment-limiting toxicity in the majority of patients. Toxicity consisted almost exclusively of mucositis. No myelosuppression or significant organ toxicity was observed. We conclude that even low doses of oral CLV potentiate the biological effect of infusion 5-FU. If the combination is to be given on a protracted basis, 5-FU must be administered at a much smaller dosage than has been traditionally utilized.