Phase I study of paclitaxel with oral etoposide in advanced solid tumors

PURPOSE: This study evaluated dose escalation of paclitaxel administered as a 3-hour infusion after a fixed oral etoposide regimen given daily for 10 days to determine an optimal dose and a toxicity profile for this combination. PATIENTS AND METHODS: Three consecutive cohorts consisting of 29 patients with measurable or assessable advanced solid tumors were treated with paclitaxel by intravenous infusion over 3 hours after receiving etoposide, 50 mg orally twice daily, for 10 days. Cycles were repeated every 28 days. Paclitaxel dose levels were: cohort 1, 135 mg/m²; cohort 2, 150 mg/m²; and cohort 3, 175 mg/m². RESULTS: Dose-limiting toxicity was observed in cohort 3 in 5 of 12 patients (4 of 12 patients met criteria for myelosuppression and 1 of 12 experienced grade 3 mucositis). No unexpected toxicities were observed, and this regimen was well tolerated. DISCUSSION: Administration of paclitaxel in combination with a prolonged oral schedule of etoposide is feasible and toxicities are manageable. The dose-limiting toxicity of a 3-hour infusion of paclitaxel after 10 days of etoposide given orally was myelosuppression. Recommended doses of this combination for phase II studies are etoposide, 100 mg orally daily for 10 days, followed by paclitaxel at a dose of 150 mg/m² intravenously over 3 hours, and repeated every 4 weeks.