Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil.
The antitumor effects of methotrexate with 5-fluorouracil against the Sarcoma 180 mouse tumor model were found to be schedule dependent. Pretreatment of tumor-bearing animals with methotrexate significantly enhanced the antitumor activity of the combination relative to simultaneous treatment or to those with methotrexate following 5-fluorouracil. These studies indirectly support the hypothesis that methotrexate pretreatment with 5-fluorouracil is synergistic by increasing the amount of thymidylate synthetase bound to the active metabolite of 5-fluorouracil.
D000818:Animals; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D012510:Sarcoma 180 / Q000188:drug therapy*; D013997:Time Factors
D005472:Fluorouracil; D008727:Methotrexate