Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: A Randomized Multicenter Phase II Trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

Purpose Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with platinum-resistant recurrent ovarian cancer. We conducted a randomized phase II trial (TOWER [ Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer]) to better define the ratio between benefits and risks with either treatment approach. Patients and Methods Patients were randomly assigned to two independent two-stage protocols of Tw (4 mg/m(2)/wk administered on days 1, 8, and 15) or Tc (1.25 mg/m(2)/d on days 1 to 5). We evaluated risk ratios (RRs) for the primary end point of clinical benefit (complete response, partial response, and stable disease), the duration of progression-free survival (PFS) and overall survival (OS), associated hazard ratios (HRs), and RRs of toxicity with 95% CIs. Results In total, 194 patients were randomly assigned at 54 centers to Tw (n = 97) or Tc (n = 97). Clinical benefit was observed in 36 of 76 (47%; 95% CI, 36% to 59%) Tw and 46 of 80 (58%; 95% CI, 46% to 68%) Tc patients (RR, 1.21; 95% CI, 0.90 to 1.64; P = .205). Patients in the Tw group had a slightly shorter PFS (HR, 1.29; 95% CI, 0.96 to 1.76) but similar OS (HR, 1.04; 95% CI, 0.74 to 1.45) compared with Tc. Tw was associated with significantly lower risks of anemia (RR, 0.35; 95% CI, 0.16 to 0.79), neutropenia (RR, 0.38; 95% CI, 0.23 to 0.65), and thrombocytopenia (RR, 0.23; 95% CI, 0.09 to 0.57). Conclusion With regard to effectiveness in terms of response and PFS, Tc remains the standard of care in patients with platinum-resistant recurrent ovarian cancer. However, comparable OS rates and a favorable toxicity profile make Tw another viable treatment option in this setting. J Clin Oncol 29:242-248. (C) 2010 by American Society of Clinical Oncology