Phase II feasibility study of sequential couplets of cisplatin/topotecan followed by paclitaxel/cisplatin as primary treatment for advanced epithelial ovarian cancer: A National Cancer Institute of Canada Clinical Trials Group Study

Purpose: Despite the improved results in advanced ovarian cancer achieved w ith the addition of paclitaxel to frontline therapy, there remains room for improvement. One approach is to add new agents such as topotecan. Because myelosuppression limits the delivery of topotecan with paclitaxel/cisplatin in a three-drug combination, we explored giving sequential couplets of cis platin/topotecan followed by paclitaxel/cisplatin. Patients and Method: Forty-four patients with residual epithelial ovarian c arcinoma after primary surgery were studied. Cisplatin 50 mg/m(2) on day 1 and topotecan 0.75 mg/m(2) on days 1 through 5 were administered at 21-day intervals for four cycles, followed by interval debulking surgery (if optim al debulking was not achieved with primary surgery), and then paclitaxel 13 5 mg/m(2) over 24 hours on day 1 and cisplatin 75 mg/m(2) on day 2 at 21-da y intervals for four cycles. Results: Such sequential couplets are feasible. Myelotoxicity was the major toxic effect, but it was of short duration. The granulocyte nadir with top otecan/cisplatin occurred late (median, day 18), so retreatment on day 21 w as not always possible. There was no unexpected nonhematologic toxicity. Th e regimen was active in this group of patients who had undergone largely su boptimal debulking surgery. In 34 patients with clinically measurable disea se, the overall response rate was 78%, and 30 (77%) of the 39 patients with elevated CA 125 levels at baseline had normalization of CA 125 levels by t he end of therapy. Conclusion: Sequential couplets of cisplatin/topotecan followed by paclitax el/cisplatin are feasible. The efficacy data in this suboptimal group of pa tients has encouraged us to proceed with a randomized study based on this a pproach. J Clin Oncol 18:4038-4044. (C) 2000 by American Society of Clinica l Oncology.