CT3 - Long-Term Normothermic Intraperitoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastasis: Results from Clinical Trials Over a Decade in Japan

Background: Intraperitoneal (ip) chemotherapy is a promising treatment option for peritoneal metastasis of gastric cancer. We have developed a new multidisciplinary treatment with long-term normothermic ip using paclitaxel (PTX) or docetaxel (DOC) via an ip port and systemic chemotherapy, combined with gastrectomy after response to chemotherapy. Here we report the results of 10 clinical trials between 2006 and 2019 and a retrospective study of surgery after response to chemotherapy. Material and methods: We performed five phase I trials with the following regimens: S-1/PTX plus ip PTX, S-1/oxaliplatin plus ip PTX, S-1/cisplatin plus ip PTX, capecitabine/cisplatin plus ip DOC, and FOLFOX plus ip PTX. We completed phase II clinical trials of the first three regimens and a multicenter phase III PHOENIX-GC trial comparing S-1/PTX plus ip PTX with standard systemic chemotherapy. Additionally, we retrospectively evaluated the results of gastrectomy in three multicenter phase II and III trials.

Results: In phase I trials, recommended doses of ip PTX and DOC were 20–40 mg/m2 and 10 mg/m2. In phase II trials, the 1-year overall survival rates were 72%–78%. PHOENIX-GC trial narrowly failed to show statistical superiority of S-1/PTX plus ip PTX over S-1 plus cisplatin (p=0.080; hazard ratio 0.72). Out of 222 patients treated with ip chemotherapy, 93 patients (42%) underwent gastrectomy. The median survival times of patients with and without surgery were 26.3 and 12.3 months respectively.

Conclusions: Multidisciplinary treatment with long-term ip and systemic chemotherapy combined with gastrectomy is safe and effective for gastric cancer patients with peritoneal metastasis.