PMID: 9420021Jan 7, 1998Paper

Biomodulation of 5-fluorouracil with antifolates

Seminars in Oncology
J R Bertino

Abstract

The cytotoxic activity of 5-fluorouracil (5-FU) can be modulated by coadministration of antifolates or leucovorin (LV). Although a recent meta-analysis concluded that a sequential combination of methotrexate (MTX) and 5-FU was superior to 5-FU alone in terms of response rate and survival, combination MTX and 5-FU therapy has not been actively pursued by many leading cancer centers. We have subsequently investigated the combination of trimetrexate (TMTX) plus 5-FU/LV. Unlike MTX, TMTX does not compete with LV for uptake or polyglutamylation. In a phase I clinical study, combination TMTX/5-FU/LV was well tolerated and produced an overall response rate of 20% in previously treated colorectal cancer patients. In a follow-up phase II clinical study, this combination was highly active in patients with advanced colorectal cancer, demonstrating a 50% overall response rate. Currently, a phase III clinical trial is in progress comparing this regimen with combination 5-FU/LV.

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