Allopurinol modulation of fluorouracil toxicity.
Considerable interest has developed in the modulation of fluorouracil activity by nucleosides. The toxicity of fluorouracil in mice is known to be reduced by concurrent administration of allopurinol, presumably because biochemical pathways activating fluorouracil in normal tissues are blocked. We have given allopurinol (300 mg t.d.s. PO) concurrently with continuous infusions of fluorouracil (2.0--2.25 g/m2/day X 5) to 34 patients with colorectal cancer and 11 patients with various adenocarcinomas. There were 41 patients assessable for toxicity. Stomatitis was the predominant dose-limiting toxicity (22% grade 1, 19% grade 2, and 27% grade 3 toxicity). Neutropenia (Less Than 1,000/mu l) occurred in 17% patients. Among 26 colorectal cancer patients assessable for response there was a 15.4% response rate. We conclude that allopurinol modulates fluorouracil toxicity in man, allowing a two-fold increase in dose. However, at least in colorectal cancer no greater frequency of tumour response is seen than with lower doses of fluorouracil given by standard schedules of administration without allopurinol.
D000493:Allopurinol / Q000627:therapeutic use*; D003875:Drug Eruptions / Q000209:etiology; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009422:Nervous System Diseases / Q000139:chemically induced; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000378:metabolism; D013280:Stomatitis / Q000139:chemically induced
D000493:Allopurinol; D009964:Orotidine-5'-Phosphate Decarboxylase; D005472:Fluorouracil