A phase 11 study to determine the efficacy and tolerability of intravenous ZD9331 in heavily pretreated patients with ovarian cancer

Background. This Phase 11, multicenter, open-label study was conducted to assess the efficacy and tolerability of ZD9331, a novel direct-acting thymidylate synthase inhibitor, in heavily pretreated patients with ovarian cancer. Methods. The study recruited 44 women with ovarian cancer or primary peritoneal cancer previously treated with platinum therapy and paclitaxel and with progressive disease after, or intolerance to, topotecan administered as the most recent therapy. ZD9331 was administered as an intravenous infusion at 130 mg/m(2) on Days I and 8 of 3-week cycles, until objective evidence of disease progression. A cutoff date of 3 months after the last patient received the first dose was set for data collection. Results. Patients received a mean of 3.3 cycles of ZD9331 and a total of 143 cycles were administered. Among the 42 patients evaluated for best overall tumor response, one achieved a complete response and two achieved a partial response, giving an objective tumor response rate of 7%. The complete response occurred at Day 15 of Cycle 2 in a patient receiving ZD9331 as her eighth-line therapy. Seven patients had stable disease, giving a disease control rate of 23%. Thirty-one patients (71%) had disease progression and the median time to progression was 53 days. Most patients (89%) experienced drug-related adverse events, most commonly nausea (73%), vomiting (48%), and neutropenia (50%). Six patients (14%) were withdrawn from treatment due to adverse events. Conclusions. The preliminary evidence of efficacy and acceptable tolerability of ZD9331 in this heavily pretreated population with ovarian cancer warrants further investigation, especially in a less heavily pretreated patient population. (C) 2003 Elsevier Inc. All rights reserved.