Ten-year follow-up of a phase 2 study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy for poor-prognosis, advanced-stage epithelial ovarian cancer

BACKGROUND: The objective of this study was to assess activity and toxicity in patients with newly diagnosed, advanced-stage epithelial ovarian cancer (EOC) who were receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. METHODS: Patients with stage III/IV EOC received cyclophosphamide 750 mg/m(2), followed by a 24-hour infusion of paclitaxel 250 mg/m(2) and cisplatin 75 mg/m(2) on Day 2. Filgrastim began on Day 3 at 10 mu g/kg daily for 9 days. Patients received 6 cycles of all drugs. Those who achieved a pathologic complete response or had microscopic residual disease at the conclusion of 6 cycles of therapy received an additional 2 to 4 cycles of paclitaxel with cyclophosphamide. Patients who had an objective response continued on cyclophosphamide and paclitaxel. RESULTS: Sixty-two patients were enrolled. Thirty-two of 62 patients had stage IIIC disease, and 26 of 62 patients had stage IV disease. According to an intent-to-treat analysis, 55 patients (89%) experienced a clinical complete remission. At a median potential follow-up of 11.4 years, the median progression-free survival was 18.9 months, and the median survival was 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with the decrease or cessation of paclitaxel. CONCLUSIONS: The studied regimen yielded a high response rate and encouraging overall survival. The current data and those reported by the Japanese Gynecologic Cincology Group suggest that further study is warranted of dose-dense or dose-intense paclitaxel regimens in women with newly diagnosed, advanced-stage EOC. Cancer 2010;116:1476-84. (C) 2070 American Cancer Society.