Intermittent continuous infusion of 5-fluorouracil and low dose oral leucovorin in patients with gastrointestinal cancer: Relationship between plasma concentrations and clinical parameters

Abstract Modulation of 5-fluorouracil (5-FU) by leucovorin and continuous infusion of 5-FU can both result in enhanced therapeutic efficacy. The main objective of this study was to determine the maximum tolerated dose (MTD) of oral leucovorin in combination with continuous infusion of 5-FU for 14 days every 4 weeks at a dose of 300 mg/ m 2 /day in 30 patients with gastrointestinal cancer. The MTD of oral leucovorin was established at 10 mg/day. Dose-limiting toxicities were mucositis, diarrhoea and hand-foot syndrome. Plasma leucovorin concentrations were below the detection limit of the assay (