A phase I study of etoposide phosphate administered as a daily 30-minute infusion for 5 days*

Publisher Website
Google Scholar
Abstract
Purpose To determine the maximum tolerated dose, toxicities, kinetics, and disposition of etoposide phosphate when administered as a daily 30‐minute infusion for 5 days. Patients and methods Twenty‐eight patients were enrolled in this phase I dose‐escalation trial. Cohorts of patients received etoposide phosphate in etoposide equivalent doses of 50, 75, 100, and 125 mg/m2 intravenously for 30 minutes each day for 5 days. Pharmacokinetic sampling of both blood and urine was performed and concentrations of etoposide and etoposide phosphate were determined on day 1 of study for each patient and on day 4 of study for three patients receiving the 100 mg/m2 dose. Results The dose‐limiting toxicity was reversible myelosuppression as evidenced by leukopenia and neutropenia. Toxicities seen were comparable to those expected from etoposide administration. With this schedule, the 100 mg/m2 dose was the maximum tolerated dose. Nonhematologic toxicities were generally mild. Two patients had major responses and three others had minor responses. Pharmacokinetic analyses revealed rapid (2. When administered as a daily 30‐minute infusion for 5 days, the dose‐limiting toxicity is myelosuppression and 100 mg/m2 daily is the maximam tolerated dose. Clinical Pharmacology & Therapeutics (1995) 57, 499–507; doi: