A phase II study to establish a referential arm for treatment of gastric cancer patients with intraperitoneal micrometastases

Abstract

15002 Background: Gastric cancer patients with free cancer cells in the peritoneal cavity as detected by cytologic examination of the peritoneal washes (CY1) are known to have dismal prognosis. In vivo studies by the authors suggest prognostic impact of early postoperative treatment with S-1 (Nakanishi H, et al. Cancer Sci 2003;94:112–8) . No standard treatment for this population has been proposed to date. Methods: A phase II study was conducted to evaluate the efficacy of S-1, a new oral fluoropyrimidine, given postoperatively to patients with CY1 disease. Eligibility criteria included histologically confirmed adenocarcinoma of the stomach without distant metastasis (peritoneal seeding allowed if completely resected), curatively resected with negative margins, <80 years of age with adequate organ functions and preoperative PS of 0∼2, and written informed consent. The primary endpoint was 2-year survival rate and secondary endpoints were time to treatment failure and safety. By referring to the historical control (2-year survival rate: 13.3%, 90% CI 3.1∼23.5%), the target 2- year survival rate was set at 36 % with estimated 90% CI>23.5%, and the sample size was calculated as 50. Results: Forty eight patients were accrued before the study was closed, and one patients was found to be ineligible (negative for the cytologic examination). Of 47 patients, 32 were men. Median age was 66 years (range: 39∼79 years). Serosal invasion was confirmed in 44 patients (94%) and node metastasis in 42 (89%). Seven patients had macroscopic but resectable peritoneal deposits. D2 dissection was encouraged and performed in 33 patients (70%). To date, median survival time was 21.7 months with 2-year survival rate of 43.5%. One patient died of ischemic heart disease 5 days after the initiation of treatment, and treatment for 7 other patients was discontinued due to toxicity. Time to treatment failure was 9.8 months and progression-free survival was 12.9 months. The most frequent >G3 toxicity was neutropenia (n=6), followed by anorexia/nausea (n=4). Conclusions: Although further period of observation is required, postoperative S-1 is likely to overwhelm the survival data obtained in the pre-S-1 era. Toxicity was manageable and 80% of the patients tolerated the treatment. No significant financial relationships to disclose.