A phase IIA study of the topoisomerase I inhibitor, exatecan mesylate (DX-895 1f), administered at two different dose schedules in patients with platinum- and taxane-resistant/refractory ovarian cancer

Objectives. There is an urgent need for new agents with activity in platinum-and taxane-resistant epithelial ovarian cancer. Exatecan mesylate is a novel topoisomerase I inhibitor with potent activity against ovarian cancer in vitro. A multicentre phase IIA study was conducted in patients with platinum- and taxane-resistant epithelial ovarian cancer. Patients and methods. Fifty-seven patients with bidimensionally measurable ovarian cancer, previously exposed to platinum and taxanes, whose disease had relapsed within 6 months of platinum-containing chemotherapy were randomised to one of two intravenous schedules of exatecan mesylate; 0.3 mg/m(2) daily for 5 days every 3 weeks (Arm A) or 2.1 mg/m(2) weekly for 3 weeks out of 4 (Arm B). Results. There were no responses in the weekly arm and a radiological response rate of 5.3% (95% CI 0.3-21.8%) in the daily arm. Principal toxicities were myelosuppression and emesis. Grade 3/4 neutropenia occurred in 29% of patients in Arm A and 6% patients in Arm B. Seventy-one percent of patients in Ann A required red cell transfusions while on treatment. Conclusions. Exatecan is well tolerated in this poor prognosis g-roup of patients but only has modest single agent activity when administered in a daily regimen. (C) 2004 Elsevier Inc. All rights reserved.