A Phase I/II Study of Dose-Escalated Ifosfamide plus Carboplatin Combination for Advanced Ovarian Carcinoma

Background: Advanced ovarian cancer is often a fatal disease, despite good initial response to chemotherapy. Dose-intense schedules have been reported, but failed to demonstrate significant breakthrough. This study evaluates high-dose ifosfamide (IFO) plus carboplatin (CBDCA) in advanced ovarian cancer. Patients and Methods: Twenty-eight patients entered this phase I/II study. All had diagnostic laparotomy and maximal debulking if possible. IFO and CBDCA were given every 3 weeks for 6 courses or less, if there was tumor progression. IFO levels ranged from 1.8 to 3 g/m(2)/day days 1-3, increasing by 0.3-g/m(2)/ day steps, and CBDCA was administered at AUC = 6. Results: An objective response (CR + PR) was obtained in 14/26 assessable patients (53.9%). The maximally tolerated dose was reached at the 2.7-g/m(2)/day IFO level. Treatment had to be terminated in 5 patients (3 with myelotoxicity, 1 with encephalopathy, and 1 refusal). Median disease-free survival time was 24.5 months, median survival time was 30 months. Conclusions: A combination of IFO 2.7 g/m(2)/day days 1-3 and CBDCA AUC = 6 can be administered safely in patients with advanced ovarian cancer. Data indicate that both response and disease-free survival rates do not differ from standard therapy.