Current studies of methotrexate and 5-fluorouracil and their interaction in human tumor cells.
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.
D000818:Animals; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000556:secondary*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D009368:Neoplasm Transplantation; D011687:Purines / Q000378:metabolism*; D011897:Random Allocation; D013936:Thymidine / Q000378:metabolism
D011687:Purines; D005472:Fluorouracil; D013936:Thymidine; D008727:Methotrexate