High-dose allopurinol modulation of 5-FU toxicity: phase I trial of an outpatient dose schedule.
In an attempt to decrease the activation of 5-FU by normal cells relative to cancer cells, 20 patients with metastatic cancer were given 72 courses of 5-FU and allopurinol (HPP) in a phase I trial. 5-FU was given daily by iv bolus injection for 5 consecutive days every 4 weeks: HPP, 300 mg orally every 8 hours for 6 consecutive days, was started 24 hours before the first injection of 5-FU. HPP appeared to modulate 5-FU toxicity by allowing higher doses (18-21 mg/kg daily for 5 days) to be given. Unexpectedly, neurotoxicity was the dose-limiting toxicity; it was slowly reversible and manifested primarily as encephalopathy, with some patients having cerebellar signs. Gastrointestinal and hematologic toxic effects were mild and infrequent. Because of the high incidence of neurotoxicity and low response rate, this program does not appear to offer any advantages over conventional dose schedules of 5-FU alone.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000493:Allopurinol / Q000008:administration & dosage* / Q000378:metabolism; D001927:Brain Diseases / Q000139:chemically induced; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000009:adverse effects* / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced
D000493:Allopurinol; D005472:Fluorouracil