INTERMITTENT CONTINUOUS-INFUSION OF 5-FLUOROURACIL AND LOW-DOSE ORAL LEUCOVORIN IN PATIENTS WITH GASTROINTESTINAL CANCER - RELATIONSHIP BETWEEN PLASMA-CONCENTRATIONS AND CLINICAL-PARAMETERS

Modulation of 5-fluorouracil (5-FU) by leucovorin and continuous infus ion 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-F U for 14 days every 4 weeks at a dose of 300 mg/m(2)/day in 30 patient s with gastrointestinal cancer. The MTD of oral leucovorin was establi shed at 10 mg/day. Dose-limiting toxicities were mucositis, diarrhoea and hand-foot syndrome. Plasma leucovorin concentrations were below th e detection limit of the assay (<0.5 mu M). Plasma 5-FU concentrations varied considerably from 0.06 to 11.3 mu M. A relation between toxici ty, response and plasma concentration of 5-FU could not be established . Our data may indicate that even very low plasma concentrations of le ucovorin are able to modulate 5-FU. In 17 patients with colorectal can cer the response rate was 24% (95% CI: 7-50%), which is comparable to other treatment schedules with leucovorin or to continuous infusion of 5-FU alone.