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

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Pooled Analysis of Fluorouracil-Based Adjuvant Therapy for Stage II and III Colon Cancer: Who Benefits and by How Much?

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.

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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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