Feasibility Study of S-1 and Intraperitoneal Docetaxel Combination Chemotherapy for Gastric Cancer with Peritoneal Dissemination

Background: Gastric cancer with cancer cells on peritoneal cytology has very poor prognosis because of the existence of simultaneous peritoneal metastasis. Here we performed a dose-escalation study of intraperitoneal docetaxel (DTX) combined with S-1 to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer with peritoneal dissemination. Patients and Methods: Twelve gastric cancer patients with positive cytology were enrolled in this study. Peritoneal lavage specimens were obtained under local anesthesia or staging laparoscopy before treatment and the combination chemotherapy was applied in patients with positive cytology. DTX was administered on day 1 intraperitoneally with initial dose of 40 mg/m 2 , stepped up to 50 or 60 mg/m 2 . S-1 was administered at a fixed dose of 80 mg/m 2 /day on days 1-14, followed by 7 days of rest. After two cycles of the combination chemotherapy, staging laparoscopy was performed to evaluate the effect of the chemotherapy. Simultaneous gastrectomy was performed in cases without peritoneal deposits at staging laparoscopy. Results: The MTD of intraperitoneal DTX was not determined and the RD was defined as 60 mg/m 2 because dose-limiting toxicity occurred in only one patient at level II (DTX: 50 mg/m 2 ). Out of twelve patients given the combination chemotherapy, nine had cytologically negative peritoneal lavage and had no peritoneal metastases at surgery after chemotherapy. Conclusion: The combined chemotherapy of S-1 plus intraperitoneal DTX was revealed to be safe and may be effective for gastric cancer with peritoneal dissemination. Although the incidence of gastric cancer has been declining, it remains the second most frequent cause of cancer-related mortality worldwide (1). The prognosis of patients with advanced gastric cancer, especially of those with serosa- invaded tumors (T3 or T4) remains poor even after curative resection, and peritoneal dissemination is one of the most common types of recurrence in such cases (2, 3).