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Current studies of methotrexate and 5-fluorouracil and their interaction in human tumor cells

Tattersall, M.H.

Seminars in Oncology 10(2 Suppl. 2): 6-14

1983

ISSN/ISBN: 0093-7754
PMID: 6867755
Document Number: 210071
Cell culture studies have indicated that the sequence of methotrexate (MTX) and 5-fluorouracil (5-FU) exposure influences cytotoxicity. Sequential MTX/5-FU shows synergistic effects in many cell lines, but the concentration of purines and thymidine are critical modulators of the outcome. Sequential 5-FU/MTX usually shows antagonistic cytotoxicity, and simultaneous MTX/5-FU is usually additive. The biochemical basis for the complex interaction of sequential MTX/5-FU is described, and studies of MTX/5-FU in tumor-bearing mice are reviewed. Sequential MTX/5-FU shows enhanced toxicity compared to other treatment sequences, but some studies suggest that the therapeutic index is not enhanced. Preliminary results of a randomized trial of sequential MTX/5-FU versus sequential 5-FU/MTX in cancer patients are presented.

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