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  • Title: Biomodulation of 5-fluorouracil with antifolates.
    Author: Bertino JR.
    Journal: Semin Oncol; 1997 Oct; 24(5 Suppl 18):S18-52-S18-56. PubMed ID: 9420021.
    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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