Prolonged topotecan infusion with cisplatin in the first-line treatment of ovarian cancer: An NYGOG and ECOG study

Objective. To determine the toxicity and efficacy of combined therapy with cisplatin and prolonged infusion topotecan as front line therapy in women with epithelial ovarian cancer. Patients and methods. Women with previously untreated, measurable and non-measurable epithelial ovarian cancer, stages Ic-IV were eligible. Patients were treated with cisplatin 75 mg/m² on day 1, followed by topotecan 0.3 to 0.4 mg/m²/day given as a continuous infusion over 14-21 days, every 28 days. Dose levels and duration of infusion were adjusted for toxicity as appropriate. Patients were evaluated for response to treatment and treatment toxicity by standard NYGOG criteria. Results. Sixty patients were enrolled. Among the 20 patients with post-surgical residual disease >2 cm, 80% [95% CI (56.3%, 94.3%)] demonstrated an objective response to therapy. The median progression-free survival for all 60 patients enrolled was 19.3 months with a median overall survival of 45.6 months given the median follow-up of 55 months (range 6-81 months). Five year survival is estimated to be 41%. Toxicity was observed in the first four patients treated with topotecan (0.4 mg/m²/day × 21 days) and dosing was continued at 0.3 mg/m²/day × 14 days thereafter. Of the 56 patients treated at the amended dose level, marrow suppression continued to be dose-limiting, with 86% of patients experiencing grade 3 or 4 neutropenia, 55% experiencing grade 3 or 4 thrombocytopenia and 50% of patients experiencing grade 3 or 4 anemia. Nonetheless, only 11/245 cycles administered were associated with febrile neutropenia and/or infection (8 port-related). Other non-hematologic toxicity was as expected. There were no treatment-related deaths. Conclusion. This large, multicenter phase II study of prolonged infusion topotecan in combination with cisplatin demonstrated similar response, time to progression and survival compared with reported results of taxane and platinum combinations. Hematologic toxicity was greater but tolerated. Further studies investigating topotecan in combination with platinum therapy as a first line agent are warranted.