Southwest Oncology Group Trial S9912: Intraperitoneal cisplatin and paclitaxel plus intravenous paclitaxel and pegylated liposomal doxorubicin as primary chemotherapy of small-volume residual stage III ovarian cancer

Abstract

Objective While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer, there is a need to develop strategies that improve the effectiveness of this approach. Methods A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin (day 8; 30–40 mg/m 2) to a regimen of intraperitoneal cisplatin (day 2; 75 mg/m 2) and intravenous (day 1; 135 mg/m 2) plus intraperitoneal (day 8; 60 mg/m 2) paclitaxel. Treatment was initially delivered on an every 3-week schedule, but was modified to an every 4-week program due to excessive toxicity. Patients were to receive 6 cycles of this regimen. Results Of 68 patients entering this trial, 63 patients were eligible and evaluable, of whom 39 (62%) completed 6 cycles. Overall, 32 (51%) experienced at least 1 grade 4 or worse toxicity (most commonly hematologic) including 5 treatment-related deaths. Median progression-free survival (PFS) was 25 months (2-year PFS: 52%) and median overall survival 51 months, an outcome similar to previous reports of cisplatin-based intraperitoneal chemotherapy in comparable patient populations. Seventeen patients (27% of all eligible patients) were without evidence of disease recurrence > 4 years following entry into the trial. Conclusion Both the overall trial outcome, and specifically the excessively severe systemic toxicity of this regimen would prevent its future development in this exact form. The provocative PFS in a subset of individuals should encourage the development of alternative strategies designed to optimize the delivery of regional therapy in ovarian cancer management.