Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

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

doi:10.1038/s41416-018-0036-7

Abstract

BackgroundWe assessed the efficacy of adding intraperitoneal (IP) chemotherapy to standard first-line intravenous (IV) chemotherapy in epithelial ovarian cancer (EOC) patients.MethodsPatients with stage IIIC-IV EOC who underwent optimal debulking surgery were randomly assigned to four cycles of weekly IP chemotherapy with cisplatin (50 mg/m2) and etoposide (100 mg/m2) followed by six cycles of IV chemotherapy every 3 weeks (IP/IV arm), or were administered IV chemotherapy alone (IV arm). The primary endpoint for this study was the 12-month non-progression rate (NPR).ResultsBetween 4/2009 and 9/2015, 218 patients were randomised, of whom 215 initiated treatment. In the IP/IV arm, 90.6% of patients completed 4 cycles of IP chemotherapy. The 12-month NPRs were 81.9% and 64.2% in the IP/IV and IV groups, respectively (HR 0.48 (95% CI 0.27–0.82)). The median progression-free survival (PFS) was increased in the IP/IV arm compared with that in the IV arm (22.4 vs. 16.8 months; HR 0.66 (0.48–0.91)) and in a subgroup with no gross cytoreduction (31.1 vs. 16.8 months; HR 0.46 (0.26–0.82)). Similar findings were detected with regard to time to first subsequent anticancer therapy (TFST) (25.9 vs. 18.0 months; P = 0.009) and time to second subsequent anticancer therapy (TSST) (40.8 vs. 30.1 months; P = 0.042). Grade 3/4 leukopenia, anaemia and gastrointestinal events were more common in the IP/IV arm, but the treatment burden was considered acceptable.ConclusionsIP chemotherapy prior to IV chemotherapy was associated with an increased 12-month NPR and a longer TSST than IV alone in patients with EOC, albeit with acceptable toxic effects. Long-term follow-up is warranted to identify the effects of IP therapy on overall survival.

Highlights

Three randomised phase 3 studies have demonstrated that cisplatin-based intraperitoneal (IP) chemotherapy is an effective management for patients with epithelial ovarian cancer (EOC) who underwent primary optimal cytoreduction[1,2,3]
Three patients in the IP/IV arm were patients were enrolled and randomised were assigned to IP/IV arm ineligible patients 2 declined to participate 1 the primary diagnosis changed to uterine papillary serous carcinoma were assigned to IV arm eligible patients Receipt of assigned IP therapy received 4 cycles (90.6%) 5 received 3 cycles 4 received 2 cycles 1 received 1 cycle
Our study confirms a practical and acceptable 28-day dose-dense weekly IP regimen with cisplatin and etoposide followed by standard IV therapy, showing that IP/IV treatment has a survival advantage over IV alone in 12-month non-progression rate (NPR), progression-free survival (PFS), to first subsequent anticancer therapy (TFST) and to second subsequent anticancer therapy (TSST)

Summary

Introduction

Three randomised phase 3 studies have demonstrated that cisplatin-based intraperitoneal (IP) chemotherapy is an effective management for patients with epithelial ovarian cancer (EOC) who underwent primary optimal cytoreduction[1,2,3]. A median 16-month improvement in overall survival (OS) was associated with cisplatin IP treatment in GOG-1723. To date, IP chemotherapy is far less utilised as a standard primary management paradigm in clinical practice[6] due to its disadvantages: higher incidence of toxicities; catheter-related complications; lower completion rate due to the inconvenience of IP administration; as well as the absence of a well-accepted optimal regimen[7]. We assessed the efficacy of adding intraperitoneal (IP) chemotherapy to standard first-line intravenous (IV) chemotherapy in epithelial ovarian cancer (EOC) patients. CONCLUSIONS: IP chemotherapy prior to IV chemotherapy was associated with an increased 12-month NPR and a longer TSST than IV alone in patients with EOC, albeit with acceptable toxic effects. Long-term follow-up is warranted to identify the effects of IP therapy on overall survival

Methods

Results

Conclusion