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Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

a , * , b , c , d , e , f , a , g , h , i , j , k , l , m , n , n , n , o , p , p , for the EORTC Gastro-Intestinal Tract Cancer Group , Cancer Research UK , Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO) , Australasian Gastro-Intestinal Trials Group (AGITG) , Fédération Francophone de Cancérologie Digestive (FFCD)

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      Summary

      Background

      Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer.

      Methods

      This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479.

      Findings

      In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group.

      Interpretation

      Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients.

      Funding

      Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.

      Related collections

      Most cited references 30

      • Record: found
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      New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.

      Anticancer cytotoxic agents go through a process by which their antitumor activity-on the basis of the amount of tumor shrinkage they could generate-has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.
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        • Record: found
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        Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.

        Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progression-free survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer. Copyright 2004 Massachusetts Medical Society
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          • Abstract: found
          • Article: not found

          Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.

          A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer. We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival. ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001). In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].). Copyright 2006 Massachusetts Medical Society.
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            Author and article information

            Affiliations
            [a ]Centre Hospitalier Universitaire Ambroise Paré, Assistance Publique Hôpitaux de Paris, Departments of Surgery and Oncology, Boulogne-Billancourt, France
            [b ]Haukeland University Hospital, University of Bergen, Department of Oncology, Bergen, Norway
            [c ]Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden
            [d ]Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
            [e ]University Hospital Aintree, Liverpool, UK
            [f ]Robert-Roessle-Klinik, Humboldt-Universität Berlin, Surgery Department, Berlin, Germany
            [g ]Klinikum der Johann-Wolfgang-Goethe-Universität, Department of General and Vascular Surgery, Frankfurt am Main, Germany
            [h ]University Department of Surgery, Southampton General Hospital, Southampton, UK
            [i ]Princess Alexandra Hospital—University of Queensland, Woolloongabba, Brisbane, Australia, Australasian Gastro-Intestinal Trials Group
            [j ]Bristol Royal Infirmary, Bristol, UK
            [k ]Hôpital Universitaire Hautepierre, Strasbourg, France
            [l ]University Hospital Birmingham, Birmingham, UK
            [m ]The Royal Infirmary of Edinburgh, Edinburgh, UK
            [n ]EORTC Data Center, Brussels, Belgium
            [o ]University Hospital Gasthuisberg, Digestive Oncology Unit, Leuven, Belgium
            [p ]Medical University Vienna, Department of Internal Medicine I and Cancer Center and Department of General Surgery, Vienna, Austria
            Author notes
            [* ]Correspondence to: Prof Bernard Nordlinger, Centre Hospitalier Universitaire Ambroise Paré, Department of Digestive Surgery, 9 avenue Charles de Gaulle, 92104 Boulogne-Billancourt, France bernard.nordlinger@ 123456apr.aphp.fr
            [‡]

            Members listed at end of paper

            Contributors
            Journal
            Lancet
            Lancet
            Lancet Publishing Group
            0140-6736
            1474-547X
            22 March 2008
            22 March 2008
            : 371
            : 9617
            : 1007-1016
            2277487
            18358928
            LANCET60455
            10.1016/S0140-6736(08)60455-9
            2008 Elsevier Ltd. All rights reserved.

            This document may be redistributed and reused, subject to certain conditions.

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            Medicine

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