TOPOTECAN IN PLATINUM-RESISTANT AND PACLITAXEL-RESISTANT OVARIAN-CANCER

Objective: The purpose of this study was to define the response rate a nd toxicity of topotecan in patients with ovarian cancer resistant to first-line therapy. Methods: Twenty patients with advanced or recurren t ovarian cancer were enrolled in a phase I/II protocol, and an additi onal 16 patients were treated following protocol closure at Washington University Medical Center. The starting dose of topotecan was 1.25 mg /m(2)/day given intravenously over 30 min for 5 consecutive days. Pati ents were eligible for response evaluation if they completed more than one cycle of topotecan. All patients were evaluated for toxicity. Res ults: Of 28 patients eligible for response evaluation, 26 were resista nt to both platinum and paclitaxel prior to treatment with topotecan. There were four partial responders and no complete responders for a to tal response rate of 14% (95% confidence interval: 4 to 33%). All resp onders had exhibited primary resistance to both platinum and paclitaxe l. Myelotoxicity was the major toxicity, with 92% of patients experien cing Gynecologic Oncology Group (GOG) grade 3 or 4 neutropenia and 67% experiencing GOG grade 3 or 4 thrombocytopenia. Other toxicity was mi nimal and easily managed. Fifty percent of patients receiving more tha n one cycle of topotecan tolerated a dose equal or greater to the star ting dose. Conclusions: Topotecan exhibits activity in patients with o varian cancer resistant to both platinum and paclitaxel. Further study is warranted in less heavily pretreated patients and in combination w ith other chemotherapeutic agents. (C) 1997 Academic Press.