Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin

Département de Chirurgie Carcinologique, Institut Gustave Roussy, Villejuif, France.
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2008; 27(5):681-5. DOI: 10.1200/JCO.2008.19.7160
Source: PubMed


To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC).
All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time.
Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test).
Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.

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    • "treatment option. The efficacy and the morbidity of this multimodality treatment highly depends on the extent of peritoneal dissemination, particularly patients with low-volume peritoneal disease and no evidence of systemic spread benefit from CRS/HIPEC (Verwaal et al, 2003; Glehen et al, 2004; Elias et al, 2009; Honore et al, 2013). It seems more effective to treat patients with a high risk of developing PC, such as pT4 or perforated stages II or III CRC. "
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    ABSTRACT: Background: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC. Methods: A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC. Results: Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed. Conclusions: The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.
    British Journal of Cancer 07/2014; 111(6). DOI:10.1038/bjc.2014.369 · 4.84 Impact Factor
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    • "The main objective of the intraperitoneal administration of chemotherapy is to heighten the concentration and the total amount of the drug, thereby reducing plasma concentrations. This treatment increased the survival of patients with carcinomatosis of colorectal origin, from pseudomyxoma and mesothelioma [8-10]. Regarding carcinomatosis of gastric origin, the results of intraperitoneal chemotherapy with conventional chemotherapeutic agents such as mitomycin C, oxaliplatin and 5FU remain disappointing. "
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    ABSTRACT: Background 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 (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/design 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.
    BMC Cancer 03/2014; 14(1):148. DOI:10.1186/1471-2407-14-148 · 3.36 Impact Factor
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    • "The HIPEC procedure is based on the principle that a high concentration of cytostatic drugs can eradicate the non-visible malignant cells in the upper layers of cells, while systemic absorption, and thereby toxicity, is limited. CRS and HIPEC may increase the 5-year survival up to 51% in selected patients with PC originating from CRC [2] and 87%-94% in patients with PMP [3,4]. "
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    ABSTRACT: Cytoreductive surgery combined with 'Hyperthermic IntraPEritoneal Chemotherapy' (HIPEC) represents the only potentially curative treatment available for carcinomatosis secondary to colorectal cancer (CRC), pseudomyxoma peritonei (PMP), malignant mesothelioma (MM) and goblet cell carcinoma (GCC). Despite preoperative investigation some patients are excluded perioperatively because of unacceptably massive tumor extent. The data available on the clinical course of these patients are sparse. This was a retrospective observational study based on records from 35 patients (21 men, 14 women) treated in a national center (Surgical Department P, Aarhus University Hospital) from June 2006 to August 2011. The study population included patients aged 18 to 70 years with CRC (n = 19), PMP (n = 11), MM (n = 3) or GCC (n = 2). Vital status was obtained by 29 November 2012. Three patients were lost to follow-up. The 30-day mortality rate was 0%. Postoperative complications within 30 days occurred in three patients (9.4%). In all, 19 patients (54%) had palliative surgery during exploratory laparotomy. In total, 28 patients (88%) received palliative chemotherapy. The median survival for CRC and PMP patients was 12.7 (95% CI 4.0 to 21.4) and 26.9 (95% CI 25.7 to 28.1) months, respectively. Exploratory laparotomy for intended curative treatment of peritoneal carcinomatosis did not imply major morbidity or mortality for patients excluded from treatment due to advanced stage of disease.
    World Journal of Surgical Oncology 09/2013; 11(1):232. DOI:10.1186/1477-7819-11-232 · 1.41 Impact Factor
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