Effect of allopurinol on the toxicity of high-dose 5-fluorouracil administered by intermittent bolus injection.
The effect of allopurinol pretreatment on the toxicity of 5-fluorouracil (5-FU) was examined in a clinical trial. Twenty-three patients were given bolus infusions of 5-FU every two weeks in doses that produced mild toxicity (0.8-1.9 g/m2). On alternate courses patients were pretreated with allopurinol either 300 mg two hours prior to and 10 hours after 5-FU, or 300 mg every 8 hours for 4 doses starting 24 hours before 5-FU. Seventeen and 20 pairs of courses were evaluable from the 2- and 24-hour pretreatment groups, respectively. Allopurinol did not produce a significant degree of protection against 5-FU-induced myelosuppression or mucositis on either dose schedule. Neurotoxicity manifesting as both cerebellar and encephalopathic signs and symptoms was the most important toxicity encountered and was dose-limiting for 5-FU on this schedule. Mean oxipurinol serum concentrations at the time of 5-FU administration were 24 microM and 104 microM for the 2- and 24-hour allopurinol pretreatment schedules respectively. Allopurinol increased the T 1/2 of 5-FU by a mean of 67% in three of the four patients studied. Pretreatment with allopurinol did not reduce the toxicity of 5-FU administered as an intravenous bolus.
D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007958:Leukocyte Count; D009092:Mucous Membrane; D009369:Neoplasms / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D010976:Platelet Count
D000493:Allopurinol; D005472:Fluorouracil