Concomitant Administration of 4-Hydroxypyrazolopyrimidine (Allopurinol) and High-Dose Continuous Infusion 5-Fluorouracil

Abstract

We tried to study the protection of allopurinol (HPP) from the toxicity of 5-fluorouracil (5-FU). A total of 29 patients received 74 cycles of chemotherapy (16 colon adenocarcinomas, 7 head and neck, 3 breast cancers and 3 cancers of pancreas). HPP was given 900 mg/day p.o. 4 days prior to treatment, and continued with same dose throughout the course of 5-FU and for 12 days after completion of the treatment. 5-FU was administered in 24 hour intravenous infusions on days 1-5 (dose range 900-1,200 mg/m2/day). 5-FU was given alone or in combination with mitomycin-C 10 mg/m2/day (1st day), epirubicin 40 mg/m2/day (1st, 2nd day), cis-platinum 120 mg/m2/day (1st day). In comparison with other studies the toxicity was limited. We conclude that HPP can diminish the side effects, especially myelosuppression, allowing an increase in the maximum tolerated dose of 5-FU; even if combined with other cytostatic drugs. Control studies must be done to confirm our observations.