Survival benefits of dose-dense early postoperative intraperitoneal chemotherapy in front-line therapy for advanced ovarian cancer: a randomised controlled study

Tingyan Shi,Yuting Luan,Huijuan Yang,Dongsheng Tu,Yunlang Cai,Zhiyuan Dai,Rongyu Zang,Xi Cheng,Jie Tang,Shumo Cai,Huaying Wang,Rong Jiang,Yuqin Zhang,Hong Pu,Ruiqin Tu,Huixun Jia

doi:10.1038/s41416-019-0543-1

Abstract

Dose-dense early postoperative intraperitoneal chemotherapy (DD-EPIC) significantly increased non-progression rate in advanced ovarian cancer (OC) patients. We report final overall survival (OS) results to further strengthen the efficacy of DD-EPIC in the front-line therapy. In this phase 2 trial, 218 patients with FIGO IIIC–IV OC were randomly allocated to receive DD-EPIC followed by intravenous (IV) chemotherapy (DD-EPIC group), or IV chemotherapy alone (IV group). The study was prespecified to detect differences in progression-free survival (PFS) and OS. At a median follow-up period of 69.1 months, the median OS was 67.5 and 46.3 months in the DD-EPIC and IV group, respectively. The probability rate of OS at 5 years was 61.0% with DD-EPIC, and 38.2% with IV (hazard ratio [HR] for death from OC, 0.70; 95% confidence interval [CI], 0.49–1.00). DD-EPIC was associated with a prolonged PFS compared with the IV group (the estimated rate of PFS at 5 years, 26.0% vs. 8.5%; HR for disease progression, 0.64; 95% CI, 0.47–0.86). DD-EPIC was associated with a longer OS than IV chemotherapy alone. It may be considered as a valuable option of the front-line therapy for advanced ovarian cancer.Trial registration: ClinicalTrials.gov, NCT01669226 (date of registration: August 20, 2012).

Highlights

To date, three randomised phase 3 clinical trials have demonstrated that intraperitoneal (IP) chemotherapy is an effective management for epithelial ovarian cancer after primary optimal debulking surgery.[1,2,3] the fourth phase 3 trial, GOG252 that reduced the cisplatin dose from 100 mg/m2 to 75 mg/m2 neither showed a survival benefit in IP Carboplatin nor in IP Cisplatin,[4] which highlights the controversy of IP chemotherapy in ovarian cancer
The probability rate of overall survival at 5 years was 61.0% with dose-dense early postoperative intraperitoneal chemotherapy (DD-early postoperative Intraperitoneal chemotherapy (EPIC)) and 38.2% with IV chemotherapy alone (HR for death from ovarian cancer, 0.70; 95% confidence interval (CI), 0.49–1.00; P = 0.047; Fig. 1a)
Patients in the DD-EPIC group showed significantly prolonged progression-free survival (PFS) compared with those in the IV group

Summary

Introduction

Three randomised phase 3 clinical trials have demonstrated that intraperitoneal (IP) chemotherapy is an effective management for epithelial ovarian cancer after primary optimal debulking surgery.[1,2,3] the fourth phase 3 trial, GOG252 that reduced the cisplatin dose from 100 mg/m2 to 75 mg/m2 neither showed a survival benefit in IP Carboplatin nor in IP Cisplatin,[4] which highlights the controversy of IP chemotherapy in ovarian cancer. Despite the increased toxicity in the DD-EPIC group, most toxicities were acceptable, and the completion rate was much higher than that in GOG172, with the infection rate. 11.6% in AICE vs 16% in GOG172, and a completion rate of IP chemotherapy 90.6% vs 42%, respectively.[2,5] The mean inpatient cost in the DD-EPIC group was not much higher than that in the control group ($9338.2 vs $7424.4)

Methods

Results

Conclusion