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 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/m2/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 (< 0.5 microM). Plasma 5-FU concentrations varied considerably from 0.06 to 11.3 microM. A relation between toxicity, response and plasma concentration of 5-FU could not be established. Our data may indicate that even very low plasma concentrations of leucovorin are able to modulate 5-FU. In 17 patients with colorectal cancer 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.
Poorter
R L
RL
University of Amsterdam, Department of Medical Oncology, The Netherlands.
Peters
G J
GJ
Bakker
P J
PJ
Taat
C W
CW
Biermans-van Leeuwe
D M
DM
Codacci-Pisanelli
G
G
Noordhuis
P
P
Oosting
J
J
Veenhof
C H
CH
D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil