BIOLOGIC EFFECTS AND SAFETY OF STAVUDINE - OVERVIEW OF PHASE-I AND PHASE-II CLINICAL-TRIALS

Data on the biologic effects and safety of stavudine in patients with AIDS and AIDS-related complex represent results of two phase I trials (n = 84), another phase I study of patients with hematologic intoleran ce to zidovudine (n = 23), and a phase II trial (n = 152). The daily d oses of stavudine ranged from 0.1 to 12.0 mg/kg. Increases in CD4 cell count, declines in serum p24 antigen, and weight gain were all relate d to the dose of stavudine. Doses of less than or equal to 2 mg/kg/day (n = 216) were well-tolerated, with a median duration of therapy of g reater than or equal to 48 weeks in the phase I studies and greater th an or equal to 79 weeks in the phase II study. The predominant dose-li miting toxicity was peripheral neuropathy, which was related to both t he dose and duration of treatment with stavudine. Elevations of liver enzymes were seen in some patients but appeared to be related to under lying disease rather than treatment. There was no evidence of dose-rel ated hematologic toxicity.