Originally published as JCO Early Release 10.1200/JCO.2004.03.087 on June 15 2004

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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Figueredo, A. Articles by Zuraw, L. Search for Related Content PubMed PubMed Citation Articles by Figueredo, A. Articles by Zuraw, L. Related Articles Related Article

Adjuvant Therapy for Stage II Colon Cancer: A Systematic Review From the Cancer Care Ontario Program in Evidence-Based Care’s Gastrointestinal Cancer Disease Site Group

From the Hamilton Regional Cancer Centre; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton; and Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada

Address reprint requests to Melissa C. Brouwers, PhD, Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St W, T-27, 3rd Floor, Hamilton, Ontario, Canada L8S 4L8; e-mail: mbrouwer{at}mcmaster.ca

Purpose: To develop a systematic review that would address the following question: Should patients with stage II colon cancer receive adjuvant therapy?

Methods: A systematic review was undertaken to locate randomized controlled trials comparing adjuvant therapy to observation.

Results: Thirty-seven trials and 11 meta-analyses were included. The evidence for stage II colon cancer comes primarily from a trial of fluorouracil plus levamisole and a meta-analysis of 1,016 patients comparing fluorouracil plus folinic acid versus observation. Neither detected an improvement in disease-free or overall survival for adjuvant therapy. A recent pooled analysis of data from seven trials observed a benefit for adjuvant therapy in a multivariate analysis for both disease-free and overall survival. The disease-free survival benefits appeared to extend to stage II patients; however, no P values were provided. A meta-analysis of chemotherapy by portal vein infusion has also shown a benefit in disease-free and overall survival for stage II patients. A meta-analysis was conducted using data on stage II patients where data were available (n = 4,187). The mortality risk ratio was 0.87 (95% CI, 0.75 to 1.01; P = .07).

Conclusion: There is preliminary evidence indicating that adjuvant therapy is associated with a disease-free survival benefit for patients with stage II colon cancer. These benefits are small and not necessarily associated with improved overall survival. Patients should be made aware of these results and encouraged to participate in active clinical trials. Additional investigation of newer therapies and more mature data from the presently available trials should be pursued.

Supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

Related Article

• American Society of Clinical Oncology Recommendations on Adjuvant Chemotherapy for Stage II Colon Cancer
  Al B. Benson, III, Deborah Schrag, Mark R. Somerfield, Alfred M. Cohen, Alvaro T. Figueredo, Patrick J. Flynn, Monika K. Krzyzanowska, Jean Maroun, Pamela McAllister, Eric Van Cutsem, Melissa Brouwers, Manya Charette, and Daniel G. Haller
  JCO 2004 22: 3408-3419 [Abstract] [Full Text]

This article has been cited by other articles:

				M. R. Somerfield, K. Einhaus, K. L. Hagerty, M. C. Brouwers, J. Seidenfeld, and G. H. Lyman American Society of Clinical Oncology Clinical Practice Guidelines: Opportunities and Challenges J. Clin. Oncol., August 20, 2008; 26(24): 4022 - 4026. [Abstract] [Full Text] [PDF]

				S. Rekhraj, O. Aziz, S. Prabhudesai, E. Zacharakis, F. Mohr, T. Athanasiou, A. Darzi, and P. Ziprin Can intra-operative intraperitoneal free cancer cell detection techniques identify patients at higher recurrence risk following curative colorectal cancer resection: a meta-analysis Ann. Surg. Oncol., January 1, 2008; 15(1): 60 - 68. [Abstract] [Full Text] [PDF]

				I. Zlobec, K. Baker, P. Minoo, J. R. Jass, L. Terracciano, and A. Lugli Node-Negative Colorectal Cancer at High Risk of Distant Metastasis Identified by Combined Analysis of Lymph Node Status, Vascular Invasion, and Raf-1 Kinase Inhibitor Protein Expression Clin. Cancer Res., January 1, 2008; 14(1): 143 - 148. [Abstract] [Full Text] [PDF]

				A. B. Benson III New Approaches to Assessing and Treating Early-Stage Colon and Rectal Cancers: Cooperative Group Strategies for Assessing Optimal Approaches in Early-Stage Disease Clin. Cancer Res., November 15, 2007; 13(22): 6913s - 6920s. [Abstract] [Full Text] [PDF]

				D. J. Sargent, S. Patiyil, G. Yothers, D. G. Haller, R. Gray, J. Benedetti, M. Buyse, R. Labianca, J. F. Seitz, C. J. O'Callaghan, et al. End Points for Colon Cancer Adjuvant Trials: Observations and Recommendations Based on Individual Patient Data From 20,898 Patients Enrolled Onto 18 Randomized Trials From the ACCENT Group J. Clin. Oncol., October 10, 2007; 25(29): 4569 - 4574. [Abstract] [Full Text] [PDF]

				P. J. O'Dwyer, S. G. Eckhardt, D. G. Haller, J. Tepper, D. Ahnen, S. Hamilton, A. B. Benson III, M. Rothenberg, N. Petrelli, H.-J. Lenz, et al. Priorities in Colorectal Cancer Research: Recommendations From the Gastrointestinal Scientific Leadership Council of the Coalition of Cancer Cooperative Groups J. Clin. Oncol., June 1, 2007; 25(16): 2313 - 2321. [Abstract] [Full Text] [PDF]

				B. M. Wolpin, J. A. Meyerhardt, H. J. Mamon, and R. J. Mayer Adjuvant Treatment of Colorectal Cancer CA Cancer J Clin, May 1, 2007; 57(3): 168 - 185. [Abstract] [Full Text] [PDF]

				S Popat, Z Chen, D Zhao, H Pan, N Hearle, I Chandler, Y Shao, W Aherne, and R. Houlston A prospective, blinded analysis of thymidylate synthase and p53 expression as prognostic markers in the adjuvant treatment of colorectal cancer Ann. Onc., December 1, 2006; 17(12): 1810 - 1817. [Abstract] [Full Text] [PDF]

				A. Barrier, P.-Y. Boelle, F. Roser, J. Gregg, C. Tse, D. Brault, F. Lacaine, S. Houry, M. Huguier, B. Franc, et al. Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling J. Clin. Oncol., October 10, 2006; 24(29): 4685 - 4691. [Abstract] [Full Text] [PDF]

				A. B. Benson III New Approaches to the Adjuvant Therapy of Colon Cancer Oncologist, October 1, 2006; 11(9): 973 - 980. [Abstract] [Full Text] [PDF]

				I Chau and D Cunningham Adjuvant therapy in colon cancer--what, when and how? Ann. Onc., September 1, 2006; 17(9): 1347 - 1359. [Abstract] [Full Text] [PDF]

				D. K. Monga and M. J. O'Connell Surgical Adjuvant Therapy for Colorectal Cancer: Current Approaches and Future Directions Ann. Surg. Oncol., August 1, 2006; 13(8): 1021 - 1034. [Abstract] [Full Text] [PDF]

				T. Andre, D. Sargent, J. Tabernero, M. O'Connell, M. Buyse, A. Sobrero, J.-L. Misset, C. Boni, and A. de Gramont Current Issues in Adjuvant Treatment of Stage II Colon Cancer Ann. Surg. Oncol., June 1, 2006; 13(6): 887 - 898. [Abstract] [Full Text] [PDF]

				M. I. Koukourakis, A. Giatromanolaki, E. Sivridis, K. C. Gatter, A. L. Harris, and for Tumour and Angiogenesis Research Group Inclusion of Vasculature-Related Variables in the Dukes Staging System of Colon Cancer Clin. Cancer Res., December 15, 2005; 11(24): 8653 - 8660. [Abstract] [Full Text] [PDF]

				N Andre and W Schmiegel CHEMORADIOTHERAPY FOR COLORECTAL CANCER Gut, August 1, 2005; 54(8): 1194 - 1202. [Full Text] [PDF]

				U. H. Frey, H. Alakus, J. Wohlschlaeger, K. J. Schmitz, G. Winde, H. G. van Calker, K.-H. Jockel, W. Siffert, and K. W. Schmid GNAS1 T393C Polymorphism and Survival in Patients with Sporadic Colorectal Cancer Clin. Cancer Res., July 15, 2005; 11(14): 5071 - 5077. [Abstract] [Full Text] [PDF]

				A. Grothey and D. J. Sargent FOLFOX for Stage II Colon Cancer? A Commentary on the Recent FDA Approval of Oxaliplatin for Adjuvant Therapy of Stage III Colon Cancer J. Clin. Oncol., May 20, 2005; 23(15): 3311 - 3313. [Full Text] [PDF]

				L. Baddi and A. Benson III Adjuvant Therapy in Stage II Colon Cancer: Current Approaches Oncologist, May 1, 2005; 10(5): 325 - 331. [Full Text] [PDF]

				S. Popat, R. Hubner, and R.S. Houlston Systematic Review of Microsatellite Instability and Colorectal Cancer Prognosis J. Clin. Oncol., January 20, 2005; 23(3): 609 - 618. [Abstract] [Full Text] [PDF]