Phase I study of VP-16-213 (Etoposide) administered as a continuous 5-day infusion

Twenty-four patients with advanced malignancy received 30 courses of VP-16-213 delivered by a protracted infusion for a minimum of 5 days or 120 hours in a phase I study to determine the maximum tolerated dose. Toxic effects included fluid overload (due to the necessary use of normal saline as the drug delivery vehicle), stomatitis, and marrow suppression with leukopenia and thrombocytopenia. Except for the stomatitis, gastrointestinal effects were virtually absent. The dose-limiting toxic effect was marrow suppression observed at a dose of 60 mg/m2/day X 5 days (300 mg/m2/course). Six of seven patients treated at this dose developed marrow suppression: 50% (three of six patients) had life-threatening leukopenia associated with fever only (one patient), sepsis (one), and septic death (one).