Bidirectional chemotherapy in gastric cancer with peritoneal metastasis combining intravenous XELOX with intraperitoneal chemotherapy with low-dose cisplatin and Doxorubicin administered as a pressurized aerosol: an open-label, Phase-2 study (PIPAC-GA2)

Background: Peritoneal metastasis (PM) develop in more than 50% of gastric cancer (GC) patients. Median survival without treatment is not more than 3-7 months, and 8-12 months after modern combination chemotherapy. Innovative therapeutic approaches are urgently needed. Methods: Phase-2, open label prospective clinical trial assessing safety and efficacy of bidirectional chemotherapy for treating peritoneal metastasis of gastric cancer (PMGC). Treatment protocol included initial staging laparoscopy or laparotomy, 3-4 courses of systemic chemotherapy (XELOX) followed by Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) procedures every 6 weeks until progression of disease or death. Primary endpoints were overall survival and histological peritoneal regression grading score after rebiopsy. Results: 31 patients were included (9 men, 22 women, mean age 52 years), 24 with synchronous PM at diagnosis, 7 with metachronous PM after previous chemotherapy. Mean PCI was 13.8 (min-max 6-34). XELOX was administered in all patients and combined with 56 PIPAC procedures. Complete and partial pathological response was found in 60% of the 15 patients eligible for tumor response assessment (4 and 5 patients, respectively). Median survival was 13 months. Conclusions: Bidirectional chemotherapy combining XELOX with PIPAC with cisplatin and doxororubicin is well tolerated, can induce objective tumor regression and is associated with a promising survival in PMGC.