HIGH-DOSE ALLOPURINOL MODULATION OF 5-FU TOXICITY - PHASE-I TRIAL OF AN OUTPATIENT DOSE SCHEDULE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (9) , 1723-1727
Abstract
To decrease the activation of 5-FU [5-fluorouracil] 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 i.v. bolus injection for 5 consecutive days every 4 wk; HPP, 300 mg orally every 8 h for 6 consecutive days, was started 24 h before the 1st 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 also having cerebellar signs. Gastrointestional 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.