Repeated normothermic intraperitoneal paclitaxel perfusion via videolaparoscopy (RIPPENC-VLP) combined with CAPOX for gastric cancer with positive cytology or limited peritoneal metastasis: A prospective phase II study.

BACKGROUND: Gastric cancer (GC) with peritoneal metastases (PM) and positive peritoneal cytology (CY+) is associated with extremely poor prognosis, and most patients are considered unsuitable for surgical treatment. We evaluated a response-adapted strategy combining repeated intraperitoneal paclitaxel perfusion via videolaparoscopy (RIPPENC-VLP) with systemic chemotherapy in patients with GC and low-volume PM. METHODS: This prospective single-center phase II study included patients with gastric adenocarcinoma presenting with positive peritoneal cytology and/or peritoneal metastases with a Peritoneal Cancer Index (PCI) ≤10. Patients received repeated normothermic intraperitoneal paclitaxel perfusion via videolaparoscopy (RIPPENC-VLP) combined with systemic capecitabine and oxaliplatin (CAPOX). Free peritoneal tumor cells were serially quantified using flow cytometry targeting CD44+/CD326+ cells. Treatment cycles were repeated every three weeks until cytological conversion and regression of peritoneal disease were achieved, allowing consideration of conversion surgery in the absence of extraperitoneal metastasis. The primary endpoint was cytological conversion (CY + to CY-). Secondary endpoints included resection rate, overall survival (OS), and safety. RESULTS: Thirty-five patients underwent 95 intraperitoneal procedures (mean 2.7 cycles per patient). Nineteen patients presented with isolated positive peritoneal cytology, whereas sixteen had macroscopic peritoneal metastases. Among patients with macroscopic peritoneal disease, the median PCI was 4 (range 1-9). Cytological conversion occurred in 27 patients (77.1%), enabling secondary gastrectomy in all converted patients. Median overall survival for the entire cohort was 24.7 months. CONCLUSIONS: Neoadjuvant intraperitoneal chemotherapy combined with systemic therapy was feasible and associated with high cytological conversion and secondary resection rates in patients with low-volume GC-PM. Serial quantification of free peritoneal tumor cells may represent a promising biomarker of locoregional response and biological selection for conversion surgery. Iterative intraperitoneal chemotherapy combined with biological monitoring may enable conversion surgery in selected patients with low-volume gastric peritoneal metastasis.