Phase I and pharmacologic study of the combination of paclitaxel, cisplatin, and topotecan administered intravenously every 21 days as first-line therapy in patients with advanced ovarian cancer

Purpose: To evaluate the feasibility of administering topotecan in combination with paclitaxel and cisplatin without and with granulocyte colony-stimulating factor (G-CSF) support as first-line chemotherapy in women with incompletely resected stage III and stage IV ovarian carcinoma. Patients and Methods: Starting doses were paclitaxel 110 mg/m(2) administered over 24 hours (day 1), followed by cisplatin 50 mg/m(2) over 3 hours (day 2) and topotecan 0.3 mg/m(2)/d over 30 minutes for 5 consecutive days (days 2 to 6). Treatment was repeated every 3 weeks. After encountering dose-limiting toxicities (DLTs) without G-CSF support, the maximum-tolerated dose was defined as 5 mu g/kg of G-CSF subcutaneously starting on day 6. Results: Twenty-one patients received a total of 116 courses at four different dose levels. The DLT was neutropenia. At the first dose level, all six patients experienced grade 4 myelosuppression. G-CSF support permitted further dose escalation of cisplatin and topotecan. Nonhematologic toxicities, primarily fatigue, nausea/vomiting, and neurosensory neuropathy, were observed but were generally mild. Of 15 patients assessable for response, nine had a complete response, four achieved a partial response, and two had stable disease. Conclusion: Neutropenia was the DLT of this combination of paclitaxel, cisplatin, and topotecan. The recommended phase 1 dose is paclitaxel 110 mg/m(2) (day 1), followed by cisplatin 75 mg/m(2) (day 2) and topotecan 0.3 mg/m(2)/d (days 2 to 6) with G-CSF support repeated every 3 weeks. (C) 1999 by American Society of Clinical Oncology.