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Originally published as JCO Early Release 10.1200/JCO.2004.09.059 on April 5 2004

Journal of Clinical Oncology, Vol 22, No 10 (May 15), 2004: pp. 1797-1806
© 2004 American Society of Clinical Oncology.
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Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer: Who Benefits and by How Much?

Sharlene Gill, Charles L. Loprinzi, Daniel J. Sargent, Stephan D. Thomé, Steven R. Alberts, Daniel G. Haller, Jacqueline Benedetti, Guido Francini, Lois E. Shepherd, Jean Francois Seitz, Roberto Labianca, Wei Chen, Stephen S. Cha, Michael P. Heldebrant, Richard M. Goldberg

From the Mayo Clinic and Mayo Foundation, Rochester, MN; British Columbia Cancer Agency, Vancouver, British Columbia; National Cancer Institute of Canada–Clinical Trials Group, Queens University, Kingston, Ontario, Canada; University of Pennsylvania Cancer Center, Philadelphia, PA; Southwest Oncology Group Statistical Center, Seattle, WA; University of Siena, Siena; Ospedali Riuniti, Bergamo, Italy; University of the Mediterranean, Marseilles and Fédération Francophone de Cancérologie Digestive, Dijon, France; University of North Carolina at Chapel Hill, Chapel Hill, NC.

Address reprint requests to Charles L. Loprinzi, MD, Medical Oncology, Mayo Clinic, 200 First St Southwest, Rochester, MN 55905; e-mail: cloprinzi{at}mayo.edu

PURPOSE: Although it is well-established that fluorouracil- (FU-) based adjuvant therapy improves survival for patients with resected high-risk colon cancer, the magnitude of adjuvant therapy benefit across specific subgroups and for individual patients has been uncertain.

PATIENTS AND METHODS: Using a pooled data set of 3,302 patients with stage II and III colon cancer from seven randomized trials comparing FU + leucovorin or FU + levamisole to surgery alone, we performed an analysis based on a Cox proportional hazards regression model. Treatment, age, sex, tumor location, T stage, nodal status, and grade were tested for both prognostic and predictive significance. Model derived estimates of 5-year disease-free survival and overall survival (OS) for surgery alone and surgery plus FU-based therapy were calculated for a range of patient subsets.

RESULTS: Nodal status, T stage, and grade were the only prognostic factors independently significant for both disease-free survival and OS. Age was significant only for OS. In a multivariate analysis, adjuvant therapy showed a beneficial treatment effect across all subsets. Treatment benefits were consistent across sex, location, age, T-stage, and grade. A significant stage by treatment interaction was present, with treatment benefiting stage III patients to a greater degree than stage II patients.

CONCLUSION: Patients with high-risk resected colon cancer obtain benefit from FU-based therapy across subsets of age, sex, location, T stage, nodal status, and grade. Model estimates of survival stratified by T stage, nodal status, grade, and age are available at http://www.mayoclinic.com/calcs. This information may improve patients' and physicians' understanding of the potential benefits of adjuvant therapy.

Supported by grant CA-25224.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

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


Related Correspondence

  • Re: Pooled Analysis of Fluorouracil-Based Adjuvant Therapy of Stage II and III Colon Cancer: Who Benefits and by How Much?
    Hany Elsaleh and Barry Iacopetta
    JCO 2005 23: 653-654 [Full Text]


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