Mature results of a phase II study of intraperitoneal topotecan as consolidation therapy in ovarian cancer

Abstract

5570 Background: Previous studies with intraperitoneal (IP) topotecan have shown 20 mg/m2 to be well tolerated. This study evaluated the feasibility, safety, and effectiveness of IP topotecan as consolidation therapy for ovarian cancer. Methods: Patients with stage III/IV ovarian (or primary peritoneal) cancer in clinical complete response after cytoreduction and IV chemotherapy with carboplatin and paclitaxel who had benign findings or minimal persistent disease (<= 1 cm diameter) documented at second-look surgery were eligible. IP topotecan 20 mg/m2 was administered once every 21 days for 4 to 6 cycles. Dose reduction was based on grade 3–4 toxicities. Hematopoietic growth factors were used at the discretion of the treating physician. Results: Twenty patients were enrolled (18 ovarian and 2 peritoneal cancers). Sixteen patients received 4 cycles, 3 patients received 6 cycles, and 1 patient withdrew by personal request after 1 cycle. Of the total 83 cycles, 10 (12%) were delayed due to slow recovery of neutropenia, and 22 (27%) were administered with does reductions due to prior grade 3–4 myelosuppression. Mean delivered dose was 18 mg/m2. Major toxicities included episodes of neutropenia (6 grade 3; 3 grade 4) and thrombocytopenia (7 grade 3; 2 grade 4). Filgrastim was administered to 75% of patients in 51 (61%) cycles, and epoetin alfa was administered to 30% of patients in 20 (24%) cycles. Other adverse events (grade 1 or 2) that occurred in approximately half of patients included nausea and abdominal distension. Median progression-free survival was 24 months from second-look surgery (Kaplan-Meier, 95% CI 14–34 months). Sixteen patients (80%) are alive after median of 42 months from second look surgery (range, 29 to 62 months), with 4.5 year estimated overall survival of 84% (95% CI 68–100%) measured from original diagnosis. Conclusion: Consolidation IP topotecan 20 mg/m2 every 3 weeks for 4–6 cycles is feasible and well tolerated. Progression-free and overall survival in this pilot study compare favorably with results expected for advanced ovarian cancer. Future investigation of IP topotecan is warranted, both as consolidation therapy and salvage therapy for advanced ovarian cancer. No significant financial relationships to disclose.