RANDOMIZED PHASE-II STUDY OF 2 SCHEDULES OF TOPOTECAN IN PREVIOUSLY TREATED PATIENTS WITH OVARIAN-CANCER - A NATIONAL-CANCER-INSTITUTE OF CANADA CLINICAL-TRIALS GROUP-STUDY

Purpose: As topotecan is S-phase-specific, its efficacy is likely sche dule-dependent. Therefore, a randomized study using a ''pick the winne r'' design was undertaken to compare two schedules in patients with re current ovarian cancer. Patients and Methods: Patients with recurrent epithelial ovarian cancer previously treated with no more than two sep arate regimens of chemotherapy, one of which had to be platinum-contai ning, were randomized to either topotecan 1.5 mg/m(2) intravenously (I V) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m(2) as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm) . Results: Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interv al [CI], 9.6% to 41.2%), which was significantly superior to that in a rm B, 3.1% (95% CI, 0.1% to 16%) (P=.026), The regimens were not equit oxic, with 94% of patients on arm A experiencing grade 3 or 4 granuloc ytopenia as opposed to 52% on arm B. Conclusion: The weekly 24 hour in fusion of topotecan at 1.75 mg/m(2) was ineffective in relapsed ovaria n cancer. The daily-times-five schedule remains the schedule of choice . As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that a lready occurs will preclude any substantially higher dosing with the w eekly regimen. (C) 1998 by American Society of Clinical Oncology.