Phase 1 study of paclitaxel administered twice weekly to children with refractory solid tumors: A Pediatric Oncology Group study

Purpose: To perform a phase 1 trial to determine the maximum tolerated dose and the dose-limiting toxicities of paclitaxel in children with refractory or recurrent solid tumors. Paclitaxel was administered twice weekly, increasing from four to six doses every 21 to 28 days. Methods: Paclitaxel was administered as a 3-hour intravenous infusion twice weekly. The initial dose was fixed at 50 mg/m²/dose twice weekly for 2 weeks (four doses), every 21 days. The number of twice-weekly doses per course was increased to six in the next cohort. In subsequent cohorts, the number of twice-weekly doses per course was fixed at six, every 28 days, and dosage was increased in 25% increments. Results: Sixteen assessable patients were enrolled at three levels. Neutropenia was the dose-limiting toxicity at 65 mg/m²/dose, twice weekly x 6 doses, every 28 days. Nonhematologic toxicities were minor. No antitumor responses were observed. Conclusions: Protracted twice-weekly dosing of paclitaxel is limited by neutropenia. The maximum tolerated dose of paclitaxel administered twice weekly x 6 doses, every 28 days, was 50 mg/m²/dose.