A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial
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Intraperitoneal administration of paclitaxel had been considered a promising option to treat peritoneal metastasis, the most frequent pattern of recurrence in gastric cancer after D2 gastrectomy, but its safety and efficacy after gastrectomy had not been fully explored.
A phase II randomized comparison of postoperative intraperitoneal (IP) vs. intravenous (IV) paclitaxel was conducted. Patients with resectable gastric linitis plastica, cancer with minimal amount of peritoneal deposits (P1), or cancer positive for the peritoneal washing cytology (CY1) were eligible. After intraoperative confirmation of the above disease status and of resectability, patients were randomized to be treated either by the IP therapy (paclitaxel 60 mg/m2 delivered intraperitoneally on days 0, 14, 21, 28, 42, 49, and 56) or the IV therapy (80 mg/m2 administered intravenously using the identical schedule) before receiving further treatments with evidence-based systemic chemotherapy. The primary endpoint was 2-year survival rate.
Of the 86 patients who were randomized intraoperatively, 83 who actually started the protocol treatment were eligible for analysis (n = 39, IP group; n = 44, IV group). The 2-year survival rate of the IP and IV groups was 64.1% (95% CI 47.9–76.9) and 72.3% (95% CI 56.3–83.2%), respectively (p = 0.5731). The IP treatment did not confer significant overall or progression-free survival benefits, and was associated with particularly poor performance in patients with residual disease, including the CY1 P0 population.
We were unable to prove superiority of the IP paclitaxel over IV paclitaxel delivered after surgery to control advanced gastric cancer with high risk of peritoneal recurrence.
KeywordsGastric cancer Intraperitoneal administration Paclitaxel Peritoneal metastasis
Paclitaxel was provided by Bristol-Myers K. K. for intraperitoneal administration in the study arm and testing of drug hypersensitivity. This study was supported, in part, by the nonprofit Epidemiological and Clinical Research Information Network (ECRIN).
Compliance with ethical standards
All procedures followed were in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1964 and later versions. Informed consent to be included in the study, or the equivalent, was obtained from all patients.
Conflict of interest disclosure statement
Dr. Yoshikawa reports grants from Japanese Foundation for Multidisciplinary Treatment of Cancer during the conduct of the study; grants and personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, and Novartis Pharmaceuticals Japan; personal fees from Abbott Japan, Ono Pharmaceutical, Eli Lilly Japan, Kaken Pharmaceutical, Yakult Honsha, Nippon Kayaku, Johnson and Johnsons, Covidien Japan, Takeda Pharmaceutical, and Olympus outside the submitted work. Dr. Sakamoto received a consulting fee from Takeda Pharmaceutical and personal fees from Tsumura and Chugai Pharmaceutical Co. Ltd outside the submitted work. Dr. Morita received personal fees from Daiichi-Sankyo and Chugai Pharmaceutical outside the submitted work. Dr. Kodera reports grants and personal fees from Taiho Pharmaceutical, Chugai Phamaceutical, Sanofi, Merck Serono, Yakult Honsha, Daiichi Sankyo, Otsuka Pharmaceutical Factory, Takeda Pharmaceutical, Kaken Pharmaceutical, Ono Pharmaceutical, Johnson & Johnson, and Eli Lilly Japan; and grants from Pfizer Japan, EA Pharma, Covidien Japan, Shionogi, Bristol Myers Squib, Japan Blood Products Organization, AbbVie GK, Eizai, Abbott Japan, CSL Behring, Tsumura, Nippon Kayaku, Novartis Pharmaceuticals Japan, KCI, Toyama Chemical, and Maruho; and personal fees from MSD, Olympus, and Asahi Kasei Pharma outside the submitted work.
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