Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian trials in ovarian cancer (MITO-1) randomized study

Abstract

Purpose: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods: To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel. © 2004 by American Society of Clinical Oncology.