Intraperitoneal Carboplatin for Ovarian Cancer — A Phase 2/3 Trial

Shoji Nagao & Takayuki Enomoto et al. · 2023-04-21

BACKGROUND: Intraperitoneal chemotherapy has been shown to be effective at reducing mortality for patients with advanced epithelial ovarian cancer but is not widely used in practice. METHODS: We performed the Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial as an open-label, international, multi-institutional, randomized phase 2/3 clinical trial in women with newly diagnosed epithelial ovarian cancer who underwent laparotomy or laparoscopy. All patients received intravenous paclitaxel (80 mg/m2 on days 1, 8, and 15 of a 21-day cycle). In addition, patients in the control group received intravenous carboplatin (dose-dense intravenous paclitaxel plus intravenous carboplatin [dd-TCiv]), whereas patients in the experimental group received dose-dense intravenous paclitaxel plus intraperitoneal carboplatin (dd-TCip). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response, treatment completion rate, and incidence of adverse events (AEs). RESULTS: Among 655 patients randomized to treatment, median (95% confidence interval [CI]) PFS was 20.7 (18.1 to 22.8) months for dd-TCiv (n=328) and 23.5 (20.5 to 26.9) months for dd-TCip (n=327; hazard ratio, 0.83; 95% CI, 0.69 to 0.99; P=0.04). The PFS benefit with dd-TCip was consistent in patients with different baseline characteristics, stage, size of residual tumor, age, and performance status. The treatment completion rates were 68.3 and 59.9% in the dd-TCiv and dd-TCip groups, respectively. The incidence of intraperitoneal catheter-related AEs in the dd-TCip group was 10.1%; there were no such AEs in the dd-TCiv group. CONCLUSIONS: In the first-line treatment of advanced epithelial ovarian cancer, intraperitoneal carboplatin resulted in a modest prolongation of PFS when given with dose-dense weekly paclitaxel regardless of residual tumor size, with no impact on noncatheter-related toxicities. (Funded by the Japan Agency for Medical Research and Development, and others; Japan Registry of Clinical Trials number, jRCTs031180141.)
Authors
Shoji Nagao, Keiichi Fujiwara, Kouji Yamamoto, Hiroshi Tanabe, Aikou Okamoto, Kazuhiro Takehara, Motoaki Saito, Hiroyuki Fujiwara, David S.P. Tan, Satoshi Yamaguchi, Sosuke Adachi, Akira Kikuchi, Takeshi Hirasawa, Takeshi Yokoi, Tomonori Nagai, Toyomi Sato, Shoji Kamiura, Akira Fujishita, Wong Wai Loong, Karen Chan, Peter Syks, Alexsander Olawaye, Sang-Young Ryu, Hiroyuki Shigeta, Eiji Kondo, Yoshihito Yokoyama, Takashi Matsumoto, Kosei Hasegawa, Takayuki Enomoto