Effect of deoxyuridine coadministration on toxicity and antitumor activity of fluorouracil and floxuridine.
The addition of deoxyuridine (UDR) to fluorouracil (FU) or floxuridine (5-fluoro-2' deoxyuridine) (FUDR) produced a substantial increase in their toxicity in BDF1 mice. Antitumor assays using sarcoma 180 tumor-bearing mice showed a concomitant increase in tumor growth inhibition for the nucleoside-drug combination over identical doses of the single drug. However, no significant increase in antitumor activity with the combination treatment was demonstrated when equitoxic doses were given. Additional support for the therapeutic equality of the single and combination drug regimens was the similarity of the therapeutic indexes for each treatment regimen involving either fluorouracil or floxuridine. The results suggested that any therapeutic benefit achieved with the combination therapy could be duplicated with either fluorouracil or floxuridine at a higher dose.
D000818:Animals; D000970:Antineoplastic Agents; D001681:Biological Assay; D003857:Deoxyuridine / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D005467:Floxuridine / Q000633:toxicity*; D005472:Fluorouracil / Q000633:toxicity*; D007928:Lethal Dose 50; D051379:Mice; D012510:Sarcoma 180 / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005467:Floxuridine; D005472:Fluorouracil; D003857:Deoxyuridine