Sequential topotecan does not improve outcomes with carboplatin-paclitaxel

Results of a randomised trial suggest that adding topotecan to carboplatin-paclitaxel does not improve overall response rates, or progression-free or overall survival in patients with advanced epithelial ovarian cancer.Combined carboplatin and paclitaxel are considered the standard of care for ovarian cancer, but long-term outlook is poor. An option is to add a third non cross reacting reagent. This prospective randomised phase III study assessed the value of adding sequential topotecan to improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer.The study included 1308 patients with previously untreated stages IIB-IV ovarian cancer who were randomised to six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top, in 658 patients) or surveillance (TC in 650 patients). The primary endpoint was overall survival.There was no significant difference between groups in median progression-free survival (18.2 months in the TC-Top arm and 18.5 months in the TC arm), median overall survival (43.1 months and 44.5 months respectively) or overall survival at 3 years (58.5% and 55.7%). Patients in the TC-Top arm had more grade 3-4 haematologic toxic effects that required more supportive care (anaemia, leukocytopenia, neutropaenia, thrombocytopaenia) and more grade 3-4 infections. They also required more blood transfusions, antibiotics and G-CSF. There was no significant difference in febrile neutropenia (3.3% and 3.1%). In the 22% of patients who had measurable disease, overall response was 69.0% in the TC-Top arm and 76.2% in the TC group, and this was also not significantly different.The authors concluded that sequential addition of topotecan to carboplatin-paclitaxel did not result improve overall response or progression-free or overall survival, but led to higher rates of haematologic toxicity and more supportive care. They suggested that a doublet combination approach of topotecan with a platinum compound may be more effective.Reference...