Perioperative intraperitoneal plus systemic chemotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gastric cancer: Phase Ib/II single-arm prospective study

Background In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis, or even after reducing peritoneal tumor burden by upfront IP chemotherapy. Method Phase Ib enrolled patients in a 3+3 dose-escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In Phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended Phase II dose (RP2D) confirmation for Phase Ib and the one-year overall survival rate for Phase II. Results The RP2D was defined as IP 175mg/m2 paclitaxel and 60mg/m2 cisplatin and oral 70mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% confidence interval [CI], 14.4-not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively. Conclusion A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.