Background: A phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal metastasis. Patients and methods: Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m² and i.p. at 20 mg/m² on days 1 and 8. S-1 was administered at 80 mg/m²/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety. Results: Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1–23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%). Conclusion: Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Objectives: A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients. Patients and Methods: Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m2, and intraperitoneally with an initial dose of 20 mg/m2, stepped up to 30 or 40 mg/m2. S-1 was administered at a fixed dose of 80 mg/m2/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed. Results: The MTD was determined to be 30 mg/m2, as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m2. The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively. Conclusions: Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials.

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m², intravenous PTX 50 mg/m² on days 1 and 8, and S-1 80 mg/m²/day on days 1-14, q3 weeks. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.