Modulation of 5-FU action by thymidine in murine and human tumors.
The biochemical basis of, and preclinical experience with, combined chemotherapy with thymidine and 5-FU are reviewed. Phase I trial and clinical pharmacologic evaluation of a monthly schedule of thymidine and 5-FU showed marked increase in the biologic activity of 5-FU. Both toxic and antitumor effects were observed. Myelosuppression was the dose-limiting side effect. The central nervous system toxicity of 5-FU appeared increased; gastrointestinal toxicity was not. The available data do not permit an assessment of whether the therapeutic index of 5-FU has been altered by combination with thymidine. The basis for the observed increase in potency of 5-FU appears to be a thymine-induced marked slowing in its catabolism that results in a prolonged plasma half-life for 5-FU and an increased cellular exposure to the drug.
D000818:Animals; D004341:Drug Evaluation; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013045:Species Specificity; D013936:Thymidine / Q000008:administration & dosage* / Q000494:pharmacology
D005472:Fluorouracil; D013936:Thymidine