Abstract
BackgroundThe peritoneum is one of the most frequent sites of recurrent gastric carcinoma after curative treatment, despite the administration of pre- and/or postoperative systemic chemotherapy. Indeed, the prognosis of peritoneal carcinomatosis from gastric carcinoma continues to be poor, with a median survival of less than one year with systemic chemotherapy. Whereas the prognosis of peritoneal carcinomatosis from colorectal cancer has changed with the development of locally administered hyperthermic intraperitoneal chemotherapy (HIPEC), survival results following carcinomatosis from gastric cancer remain disappointing, yielding a 5-year survival rate of less than 20%. Innovative surgical therapies such as intraperitoneal immunotherapy therefore need to be developed for the immediate postoperative period after complete cytoreductive surgery. In a recent randomised study, a clinical effect was obtained after intraperitoneal infusion of catumaxomab in patients with malignant ascites, notably from gastric carcinoma. Catumaxomab, a nonhumanized chimeric antibody, is characterized by its unique ability to bind to three different types of cells: tumour cells expressing the epithelial cell adhesion molecule (EpCAM), T lymphocytes (CD3) and also accessory cells (Fcγ receptor). Because the peritoneum is an immunocompetent organ and up to 90% of gastric carcinomas express EpCAM, intraperitoneal infusion of catumaxomab after complete resection of all macroscopic disease (as defined in the treatment of carcinomatosis from colorectal cancer) could therefore efficiently treat microscopic residual disease.Methods/designThe aim of this randomized phase II study is to assess 2-year overall survival after complete resection of limited carcinomatosis synchronous with gastric carcinoma, followed by an intraperitoneal infusion of catumaxomab with different total doses administered in each of the 2 arms. Close monitoring of peri-opertive mortality, morbidity and early surgical re-intervention will be done with stopping rules. Besides this analysis, translational research will be conducted to determine immunological markers of catumaxomab efficacy and to correlate these markers with clinical efficacy.
Highlights
The peritoneum is one of the most frequent sites of recurrent gastric carcinoma after curative treatment, despite the administration of pre- and/or postoperative systemic chemotherapy
A meta-analysis reported that systemic chemotherapy extended median survival time to 11 months in patients with advanced gastric cancer compared to the best supportive care alone [25]
In an attempt to improve the prognosis of such patients operated on for gastric carcinoma, prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been evaluated in patients at higher risk of developing peritoneal recurrence
Summary
Rationale Peritoneal carcinomatosis from gastric carcinoma the incidence of gastric cancer has decreased during the past years, it is still the fourth most common newly diagnosed cancer worldwide and the second leading cause of cancer-related death [1]. Median survival was significantly longer in the group of patients who developed HAMAs (129 vs 64 days, p = 0.0003; hazard ratio 0.433) These results demonstrate that there was a strong correlation between humoral immune response to catumaxomab and clinical outcome in that phase II/III study. The original concept of this study is to undertake the initial treatment combining surgery treating the visible disease (macroscopic) and intraperitoneal immunotherapy treating the remaining invisible (microscopic) disease The latter will be administered via a continuous peritoneal infusion over 6 days postoperatively with 3 injections of catumaxomab every 48 hours at increasing doses in order to limit systemic inflammatory reactions. The study was assigned the EudraCT number 2012-000475-174 and is registered at ClinicalTrials.gov (NCT01784900)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
