Biologic effects and safety of stavudine: overview of phase I and 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 intolerance to zidovudine (n = 23), and a phase II trial (n = 152). The daily doses 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 related to the dose of stavudine. Doses of < or = 2 mg/kg/day (n = 216) were well-tolerated, with a median duration of therapy of > or = 48 weeks in the phase I studies and > or = 79 weeks in the phase II study. The predominant dose-limiting toxicity was peripheral neuropathy, which was related to both the dose and duration of treatment with stavudine. Elevations of liver enzymes were seen in some patients but appeared to be related to underlying disease rather than treatment. There was no evidence of dose-related hematologic toxicity.