5-Fluorouracil dose intensity increase in 5-fluorouracil and leucovorin combination: results of a phase II study.

It was our intention to verify if in the combination of 5-fluorouracil and leucovorin, the fluoropyrimidine dose intensity is an important determinant of response as noted by Hryniuk when 5-fluorouracil was given alone. By employing the Machover regimen but with cycles repeated every three weeks, a 5-fluorouracil projected dose intensity of 616 mg/m2/wk was obtained. It approximates the maximum tolerated dose for this drug when used alone by i.v. bolus. 50 patients entered this study and 48 were evaluable for response and toxicity. The overall response rate was 29% (five complete responses and nine partial responses). The dose limiting toxicity was gastrointestinal rather than myelosuppression. 5-fluorouracil dose reduction was needed in seven patients. The mean delivered dose intensity of 5-fluorouracil was 610 mg/m2/wk (582 mg/m2/wk in patients in whom 5-fluorouracil was reduced for toxicity and 616 mg/m2/wk in the others). Our results do not seem to show any advantage in the maximization of 5-fluorouracil dose intensity. Furthermore, in an analysis of data from the literature we did not find any difference in response rate in relation to dose intensity in the 5-fluorouracil/leucovorin combination.