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Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.

ABSTRACT: 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. 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 (Fc? 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.The 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.

SUBMITTER: Goere D

PROVIDER: S-EPMC3973895 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.

Goéré Diane D Gras-Chaput Nathalie N Aupérin Anne A Flament Caroline C Mariette Christophe C Glehen Olivier O Zitvogel Laurence L Elias Dominique D

BMC cancer 20140304

<h4>Background</h4>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. 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 administe ...[more]

PMID: 24589307

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Project description:BackgroundPeritoneal carcinomatosis (PC) is a common endpoint in both gastrointestinal and non-gastrointestinal cancers, and PC is treated as other systemic metastases - unfortunately with disappointing results and considerable side-effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a new method of applying traditional chemotherapy, and preliminary data indicate that PIPAC is safe, able to stabilize or improve quality of life, and can induce an objectively measurable reduction in disease burden in PC.MethodsPIPAC-OPC2 is a prospectively controlled Phase II, single center, one-arm, open-label clinical trial investigating the treatment effect of PIPAC in patients with histological or cytological proven PC from gastrointestinal, ovarian or primary peritoneal cancer. Eligible patients will receive PIPAC in series of three using a combination of doxorubicin (1.5 mg/m2) and cisplatin (7.5 mg/m2) for non-colorectal cancer patients (PIPAC C/D), and oxaliplatin (92 mg/m2) in patients with PC of colorectal origin (PIPAC OX). Patients are monitored by: (1) repeated measurements of the Peritoneal Regression Grading Score (PRGS) in biopsies obtained from metal clips marked areas, (2) Quality-of-Life (QoL) questionnaires, (3) Magnetic Resonance Imaging (MRI) and (4) Prognostic Nutritional Index (PNI). Adverse events and surgical complications will be recorded according to the 30 days definition.ResultsThe primary outcome of PIPAC-OPC2 is to evaluate if PIPAC can induce major or complete response (PRGS 1 or 2) within a series of three PIPAC procedures. Secondarily this study investigates changes in QoL and MRI as a staging and response evaluation tool. The secondary outcomes will be used to create a model that may predict which of the patients will benefit from PIPAC treatment.ConclusionsIt is expected that PIPAC directed therapy can induce major or complete response in 50 % of patients with PC of colorectal origin and in 30 % of patients with PC of non-colorectal origin - and at the same time stabilize or even improve quality of life. This trial may provide data regarding the utility of MRI as a staging and response evaluation tool in patients with PC.Trial registrationThe study is registered with ClinicalTrials.gov Identifier NCT03287375 and the European Clinical Trials Database (EudraCT) number 2016-003394-18.

Project description:BackgroundGastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting.MethodsWe constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n = 10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases.ResultsIn the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model.ConclusionsThe presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

Dataset Information

Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.

Publications

Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab.

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