Phase 2 evaluation of topotecan administered on a 3-day schedule in the treatment of platinum- and paclitaxel-refractory ovarian cancer

Purpose. The aim of this study was to investigate the toxicity and efficacy of a more convenient topotecan administration schedule tin contrast to the "standard" 1.5 mg/m(2)/day x 5 days q 21 days) in the management of platin um- and paclitaxel-refractory ovarian cancer. Methods. Patients with clinically defined platinum- and paclitaxel-refracto ry ovarian cancer participating in this phase 2 trial conducted by the Gyne cologic Cancer Program of the Cleveland Clinic Taussig Cancer Center receiv ed topotecan at a dose of 1.5 mg/m(2)/day x 3 days on a 21-day schedule. Bo th 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 me dian of two prior regimens (range: 1-4) (retreatment with a platinum agent or palcitaxel considered a single regimen). The median number of topotecan courses delivered was 3 (range: 1-7). Major toxicity included grade 4 neutr openia (24% of patients); neutropenic fever (10%); grade 3 thrombocytopenia (10%); and requirement for blood transfusion (14%). Dose escalation was po ssible, and dose reductions required, in 14 and 28% of patients, respective ly. Two patients exhibited evidence of a clinically relevant response to tr eatment. 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 infu sion schedule in platinum/paclitaxel-refractory ovarian cancer. Further inv estigation will be required to document the clinical utility of a 3-day top otecan schedule in a less heavily pretreated and more chemosensitive patien t population. (C) 2000 Academic Press.