Background: The addition of intraperitoneal (IP) paclitaxel (PTX) to systemic chemotherapy comprising taxane/fluoropyrimidine doublet has shown promising results for patients with gastric cancer (GC) and peritoneal metastases (PM). However, this has not been studied in combination with platinum/fluoropyrimidine doublet which is the current standard-of-care for metastatic GC. We conducted a prospective phase 2 trial of IP PTX with capecitabine and oxaliplatin (XELOX) in patients with GCPM. Methods: The trial enrolled 44 patients with GCPM who received treatment comprising IP PTX (40mg/m² on day 1,8), PO capecitabine (1000mg/m² twice daily from day 1-14) and IV oxaliplatin (100mg/m² on day 1) in 21-day cycles. Patients with synchronous GCPM were eligible for conversion surgery comprising radical gastrectomy if they had good response after chemotherapy, negative cytology on 2 consecutive peritoneal fluid assessments, no extraperitoneal metastasis and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were also compared with a retrospective cohort of 39 patients with GCPM who received identical systemic chemotherapy (SC) comprising platinum/fluoropyrimidine agents alone. Results: The median OS for the IP and SC groups was 14.6 and 10.6 months (HR 0.44; 95% CI, 0.26-0.74; P=0.002). The 1-year OS was 67.8% in the IP group and 32.3% in the SC group (Logrank p<0.001). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI, 0.25-0.66; P<0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p=0.021) and had better baseline performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p=0.007) compared to the IP cohort. In the IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95%CI 13.1 – 35.3) months and 1-year OS of 84.6%. Wound-related complications requiring the port to be explanted or re-sited occurred in 9% (4/44) of patients. Conclusions: IP PTX with XELOX is a promising treatment option for GCPM patients. For patients with good response, conversion surgery was feasible with favourable outcomes. Clinical trial information: NCT01739894

* Cox proportion hazard with reference to systemic chemotherapy group.