Topotecan weekly versus routine 5-day schedule in patients with platinum-resistant ovarian cancer (TOWER): A randomized, multicenter trial of the North-Eastern German Society of Gynecological Oncology (NOGGO)

Abstract

5553 Background: In women with platinum-resistant recurrent ovarian cancer, weekly administration of topotecan (Tw) may be equally effective, but better tolerated than conventional 5-day dosing (Tc). We conducted a randomized multicenter trial to validate this assumption. Methods: The trial was pre-registered at clinicaltrials.gov ( NCT00170677 ). Women with platinum-resistant ovarian and fallopian tube cancers or primary peritoneal carcinoma, and measurable or assessable disease (GCIG criteria) were randomized to receive either Tw (d1,8,15/q28d, 4 mg/m2) or Tc (d1–5/q21d, 1.25 mg/m2). The predefined stopping rule, based on the primary endpoint of best CA-125 or tumor response, was not reached (presented at ASCO 2007, Abstract 5526). This permitted the accrual of 194 patients, 154 of whom could be assessed for CA-125 or tumor response (SD + CR + PR). We also compared progression-free (PFS) and overall survival (OS), as well as toxicity between trial groups. Results: Mean age was 61.8 (SD 9.8) years, and 59 women were on third-line treatment. Patients received a total of 809 cycles of chemotherapy. Demographic baseline characteristics, tumor stages and grades, and previous lines of chemotherapy were well balanced between treatment groups. There were 35 / 75 (47%) and 45 / 79 (57%) responses in the Tw and Tc groups, respectively (risk ratio [RR] 1.22, 95% CI 0.89–1.66). Median PFS and OS did not differ markedly between both regimens (3.2 versus 4.4 months, hazard ratio [HR] 1.30, 95% CI 0.96–1.77 and 9.8 versus 10.0 months, HR 1.08, 95% CI 0.77–1.52). The risk of grade III/IV hematological toxicity was significantly lower in the Tw group (anemia: RR 0.35, p = 0.007, neutropenia: RR 0.38, p = 0.0001, thrombopenia: RR 0.23, p = 0.0004). Conclusions: Weekly administration of topotecan shows no substantial difference in endpoints of effectiveness compared to conventional dosing, but is associated with a significantly lower likelihood of severe hematological toxicity. Weekly topotecan should be considered as a possible treatment alternative in women with platinum-resistant ovarian cancer because of its favourable benefit-risk-profile. No significant financial relationships to disclose.