Phase 2 Evaluation of Topotecan Administered on a 3-Day Schedule in the Treatment of Platinum- and Paclitaxel-Refractory Ovarian Cancer

Abstract

Purpose. The aim of this study was to investigate the toxicity and efficacy of a more convenient topotecan administration schedule (in contrast to the “standard” 1.5 mg/m²/day × 5 days q 21 days) in the management of platinum- and paclitaxel-refractory ovarian cancer.

Methods. Patients with clinically defined platinum- and paclitaxel-refractory ovarian cancer participating in this phase 2 trial conducted by the Gynecologic Cancer Program of the Cleveland Clinic Taussig Cancer Center received topotecan at a dose of 1.5 mg/m²/day × 3 days on a 21-day schedule. Both dose escalations and reductions were permitted in the protocol design.

Results. A total of 29 patients (median age: 61; range: 43–80) were treated with this modified topotecan schedule. These individuals had received a median of two prior regimens (range: 1–4) (retreatment with a platinum agent or paclitaxel considered a single regimen). The median number of topotecan courses delivered was 3 (range: 1–7). Major toxicity included grade 4 neutropenia (24% of patients); neutropenic fever (10%); grade 3 thrombocytopenia (10%); and requirement for blood transfusion (14%). Dose escalation was possible, and dose reductions required, in 14 and 28% of patients, respectively. Two patients exhibited evidence of a clinically relevant response to treatment.

Conclusion. This 3-day topotecan program is more convenient and less toxic than the standard 5-day regimen. The limited level of activity observed is not inconsistent with that previously reported for the 5-day topotecan infusion schedule in platinum/paclitaxel-refractory ovarian cancer. Further investigation will be required to document the clinical utility of a 3-day topotecan schedule in a less heavily pretreated and more chemosensitive patient population.