Originally published as JCO Early Release 10.1200/JCO.2008.17.3781 on September 15 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitry, E. Articles by Rougier, P. Search for Related Content PubMed PubMed Citation Articles by Mitry, E. Articles by Rougier, P. Related Articles Related Editorial Social Bookmarking                            What's this?

Adjuvant Chemotherapy After Potentially Curative Resection of Metastases From Colorectal Cancer: A Pooled Analysis of Two Randomized Trials

Emmanuel Mitry, Anthony L.A. Fields, Harry Bleiberg, Roberto Labianca, Guillaume Portier, Dongsheng Tu, Donato Nitti, Valter Torri, Dominique Elias, Chris O'Callaghan, Bernard Langer, Giancarlo Martignoni, Olivier Bouché, Franck Lazorthes, Eric Van Cutsem, Laurent Bedenne, Malcolm J. Moore, Philippe Rougier

From the Hôpital Ambroise Paré, Assistance Publique Hôpitaux de Paris, Boulogne and EA4340, Faculty of Medicine, Paris-Ile de France Ouest, Université Versailles, Saint-Quentin; Centre Hospitalier Universitaire Purpan, Toulouse; Institut Gustave Roussy, Villejuif; Centre Hospitalier Universitaire Robert Debré, Reims; and Centre Hospitalier Universitaire Dijon and Fédération Francophone de Cancérologie Digestive, Dijon, France; University of Toronto, and Princess Margaret Hospital, Toronto; National Cancer Institute of Canada Clinical Trials Group, Queens University, Kingston, Ontario; and Alberta Cancer Board, Edmonton, Alberta, Canada; Institute Jules Bordet, Brussels; Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium; Ospedali Riuniti, Bergamo; University of Padova, Padova; and Ospedale San Carlo Borromeo, Milano, Italy

Corresponding author: Emmanuel Mitry, MD, PhD, Hépato-gastroentérologie et oncologie digestive, Hôpital Ambroise Paré, 9 ave Charles de Gaulle, 92100 Boulogne, France; e-mail: emmanuel.mitry{at}apr.aphp.fr

Purpose Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.

Patients and Methods After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m² administered intravenously [IV] once daily plus DL-leucovorin 200 mg/m² [FFCD] x 5 days or FU 370 mg/m² plus L-leucovorin 100 mg/m² IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm).

Results A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis.

Conclusion This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus–based regimen after complete resection of colorectal cancer metastases.

published online ahead of print at www.jco.org on September 15, 2008.

Supported by Association pour la Recherche en Oncologie Digestive.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Editorial

• Perioperative or Adjuvant Therapy for Resectable Colorectal Hepatic Metastases
  Nicholas J. Petrelli
  JCO 2008 26: 4862-4863 [Full Text]

This article has been cited by other articles:

				S. Ogino, K. Nosho, N. Irahara, K. Shima, Y. Baba, G. J. Kirkner, J. A. Meyerhardt, and C. S. Fuchs Prognostic Significance and Molecular Associations of 18q Loss of Heterozygosity: A Cohort Study of Microsatellite Stable Colorectal Cancers J. Clin. Oncol., September 20, 2009; 27(27): 4591 - 4598. [Abstract] [Full Text] [PDF]

				A. Grothey Review: Medical treatment of advanced colorectal cancer in 2009 Therapeutic Advances in Medical Oncology, September 1, 2009; 1(2): 55 - 68. [Abstract] [PDF]

				D. J. Gallagher and N. E. Kemeny Colorectal Hepatic Metastases: Adjuvant Chemotherapy and Survival J. Clin. Oncol., July 10, 2009; 27(20): e18 - e19. [Full Text] [PDF]

				M. Ychou, W. Hohenberger, S. Thezenas, M. Navarro, J. Maurel, C. Bokemeyer, E. Shacham-Shmueli, F. Rivera, C. Kwok-Keung Choi, and A. Santoro A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer Ann. Onc., June 30, 2009; (2009) mdp236v1. [Abstract] [Full Text] [PDF]

				J. Pfannschmidt Invited Commentary. Ann. Thorac. Surg., June 1, 2009; 87(6): 1688 - 1689. [Full Text] [PDF]

				B. Nordlinger, E. Van Cutsem, T. Gruenberger, B. Glimelius, G. Poston, P. Rougier, A. Sobrero, M. Ychou, and on behalf of the European Colorectal Metastases Tr Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel Ann. Onc., June 1, 2009; 20(6): 985 - 992. [Abstract] [Full Text] [PDF]

				D. G. Power and N. E. Kemeny The role of floxuridine in metastatic liver disease Mol. Cancer Ther., May 1, 2009; 8(5): 1015 - 1025. [Abstract] [Full Text] [PDF]

				N. J. Petrelli Perioperative or Adjuvant Therapy for Resectable Colorectal Hepatic Metastases J. Clin. Oncol., October 20, 2008; 26(30): 4862 - 4863. [Full Text] [PDF]