Failure of allopurinol to provide clinically significant protection against the hematologic toxicity of a bolus 5-FU schedule

Allopurinol has been shown to ameliorate the myelotoxicity of 5-fluorouracil (5-FU) given as an infusion. To study the potential effectiveness of allopurinol in modifying the toxicity of 5-FU given as a bolus, 8 adult patients with metastatic malignancies were given 11 courses of bolus 5-FU with allopurinol. Allopurinol was administered at a dose of 900 mg/day orally beginning a week prior to the 5-FU therapy and continued a week after the last dose of 5-FU was administered. Three patients received a total of 5 courses of 600 mg/m² of 5-FU via bolus injection for 4 consecutive days every 28 days. Six patients were given 6 courses of 800 mg/m² of 5-FU via bolus injection in the same schedule. Gastrointestinal toxicity was mild and no significant neurotoxicity was documented. However, severe myelosuppression occurred at the 800 mg/m² dosage which led to marked leukopenia in 5 of the 6 patient courses and thrombocytopenia in 1. Gram-negative sepsis developed in 3 of the leukopenic patients with 2 resultant deaths. Allopurinol does not appear to allow clinically significant dose escalation of bolus 5-FU given on this schedule.