Carboplatin and paclitaxel in ovarian carcinoma: A phase I study of the Gynecologic Oncology Group

Purpose: To develop a tolerable, dose-intense regimen of carboplatin and paclitaxel for the treatment of primary epithelial ovarian carcinoma. Patients and Methods: Patients underwent initial surgical assessment and tumor debulking. patients with stage III/IV disease received six cycles of chemotherapy on a planned 21-day cycle. Carboplatin dose was calculated based on projected area under the curve (AUG) for concentration over time (mg . mL(-1). min) and escalated to determine the maximum-tolerated dose (MTD). Paclitaxel dose was also escalated as a 3-, 24-, or 96-hour infusion, Granulocyte colony-stimulating factors (G-CSFs) were required at selected dose levels or could be added based on hematologic toxicity. Results: Thirty-nine patients were enrolled and assessable for toxicity and response. Dose-limiting toxicity (DLT) was hematologic, primarily neutropenia. Less than 2% of all cycles with paclitaxel as a 3- or 24-hour infusion were associated with either grade 4 thrombocytopenia or febrile neutropenia. The carboplatin MTD was AUC 7.5 (equivalent to a median dose of 471 mg/m(2)). The MTD for paclitaxel was 135 mg/m(2) over 24 hours and 175 mg/m(2) over 3 hours without initial G-CSF. A 96-hour infusion of paclitaxel at a dose of 120 mg/m(2) was associated with excessive single-cycle and cumulative myelosuppression, and was not further evaluated, Measured carboplatin AUC agreed well with the calculated AUC. The overall complete (n = 16) and partial (n = 2) response rate among 24 patients with measurable disease was 75%, with a median progression-free survival time of 15 months. Conclusion: Carboplatin could be safely combined with paclitaxel using a dose formula based on projected renal clearance, The recommended outpatient regimen is carboplatin AUC 7.5 and paclitaxel 175 mg/m(2) over 3 hours without initial G-CSF. This treatment safely achieved a greater dose-intensity of carboplatin than would have been achieved with conventional dosing based on body-surface area. (C) 1996 by American Society of Clinical Oncology.