Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown in ovarian cancer. We developed a regimen combining IP PTX with S-1/PTX for the treatment of gastric cancer, and obtained promising results with a one-year overall survival (OS) rate of 78% in a phase II study. This phase III study evaluated the efficacy of IP PTX plus S-1/PTX compared to standard systemic chemotherapy.
Eligibility criteria included pathologically confirmed gastric adenocarcinoma, peritoneal metastasis, and no or short-term (
Between October 2011 and November 2013, 183 patients were enrolled, and 164 patients were included in the efficacy analysis. Baseline characteristics were balanced between the two arms except for ascites. Of 45 patients with ascites beyond the pelvic cavity, 38 (84%) were randomized to the IP arm and 7 (16%) to the SP arm. The median OS for IP and SP were 17.7 and 15.2 months, respectively (stratified log-rank test, p = 0.080; hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.49-1.04, p = 0.081). For a sensitivity analysis using a stratified Cox regression model, adjusting for the baseline ascites, the HR was 0.59 (95%CI 0.39-0.87, p = 0.0079). The response rate was 53% in the IP arm, and 60% in the SP arm (p = 1.0). In the subgroup analysis, the IP arm showed longer OS in female patients, patients with histologically undifferentiated tumors and patients with ascites beyond the pelvic cavity. Both regimens were tolerable.
The primary analysis did not show the statistical superiority of the IP regimen. The sensitivity analysis, considering the imbalance of ascites, suggested clinical efficacy of IP PTX in gastric cancer with peritoneal metastasis.
Clinical trial identification
Legal entity responsible for the study
The University of Tokyo
Japan Agency for Medical Research and Development
H. Ishigami: Research Funding: Taiho Pharmaceutical, Chugai Pharma. R. Fukushima: Research Funding: Chugai Pharma, Taiho Pharmaceutical, Aventis Pharma. Y. Kodera: Research Funding: Chugai Pharma, Daiichi Sankyo, Bristol-Myers Squibb Japan, Otsuka Pharmaceutical Factory, Taiho Pharmaceutical, Takeda, Eisai, Johnson & Johnson, Abbott Japan, Abbvie, Shionogi, Sanofi, CSL Behring, Yakult, Lilly Japan, and others. Y. Uenosono: Research Funding: Chugai Pharma. K. Amagai: Consulting or Advisory Role: Taiho Pharmaceutical, Yakult, Honsha. S. Kadowaki: Research Funding: Lilly, Taiho Pharmaceutical. J. Kitayama: Research Funding: Taiho Pharmaceutical. All other authors have declared no conflicts of interest.