Originally published as JCO Early Release 10.1200/JCO.2006.08.2974 on April 30 2007

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Oxaliplatin Combined With Weekly Bolus Fluorouracil and Leucovorin As Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: Results From NSABP C-07

J. Philip Kuebler, H. Samuel Wieand, Michael J. O'Connell, Roy E. Smith, Linda H. Colangelo, Greg Yothers, Nicholas J. Petrelli, Michael P. Findlay, Thomas E. Seay, James N. Atkins, John L. Zapas, J. Wendall Goodwin, Louis Fehrenbacher, Ramesh K. Ramanathan, Barbara A. Conley, Patrick J. Flynn, Gamini Soori, Lauren K. Colman, Edward A. Levine, Keith S. Lanier, Norman Wolmark

From the National Surgical Adjuvant Breast and Bowel Project Operations Office and Biostatistical Center; Department of Biostatistics, University of Pittsburgh, Graduate School of Public Health; Allegheny General Hospital; Division of Hematology/Oncology, University of Pittsburgh, Cancer Institute; Department of Medicine, University of Pittsburgh, Pittsburgh, PA; Columbus Community Clinical Oncology Program (CCOP), Columbus, OH; Department of Surgery, Helen F. Graham Cancer Center, Newark, DE; Australasian Gastro-Intestinal Trials Group, University of Sydney, Sydney, Australia; Atlanta Cancer Care, Atlanta, GA; Southeast Cancer Control Consortium, Goldsboro; Surgical Oncology Service, Wake Forest University, Winston-Salem, NC; Division of Surgical Oncology, Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center, Baltimore, MD; Cancer Research for the Ozarks (CCOP), Springfield, MO; Hematology/Oncology Department, Kaiser Permanente, Northern California, Vallejo, CA; Division Hematology/Oncology, Department of Medicine, Michigan State University, East Lansing, MI; Metro-Minnesota CCOP, Minneapolis, MN; CCOP Missouri Valley Cancer Consortium, Omaha, NE; Northwest CCOP, Tacoma, WA; and the Columbia River Oncology Program, Portland, OR
Deceased

Address reprint requests to Michael J. O'Connell, MD, NSABP East Commons Professional Bldg, Four Allegheny Center, Pittsburgh, PA 15212; e-mail: michael.o'connell{at}nsabp.org

Purpose This phase III clinical trial evaluated the impact on disease-free survival (DFS) of adding oxaliplatin to bolus weekly fluorouracil (FU) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer.

Patients and Methods Patients who had undergone a potentially curative resection were randomly assigned to either FU 500 mg/m² intravenous (IV) bolus weekly for 6 weeks plus leucovorin 500 mg/m² IV weekly for 6 weeks during each 8-week cycle for three cycles (FULV), or the same FULV regimen with oxaliplatin 85 mg/m² IV administered on weeks 1, 3, and 5 of each 8-week cycle for three cycles (FLOX).

Results A total of 2,407 patients (96.6%) of the 2,492 patients randomly assigned were eligible. Median follow-up for patients still alive is 42.5 months. The hazard ratio (FLOX v FULV) is 0.80 (95% CI, 0.69 to 0.93), a 20% risk reduction in favor of FLOX (P < .004). The 3- and 4-year disease-free survival (DFS) rates were 71.8% and 67.0% for FULV and 76.1% and 73.2% for FLOX, respectively. Grade 3 neurosensory toxicity was noted in 8.2% of patients receiving FLOX and in 0.7% of those receiving FULV (P < .001). Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5% of the patients receiving FLOX and in 3.0% of the patients receiving FULV (P < .01). A total of 1.2% of patients died as a result of any cause within 60 days of receiving chemotherapy, with no significant difference between regimens.

Conclusion The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer. FLOX can be recommended as an effective option in clinical practice.

published online ahead of print at www.jco.org on April 30, 2007.

Supported by Public Health Service Grants No. U10-CA-12027, U10-CA-37377, U10-CA-69974, and U10-CA-69651 from the National Cancer Institute, Department of Health and Human Services.

Clinical Trial Registry Information: ClinicalTrials.gov ID#: NCT00004931, http://clinicaltrial.gov/ct/shows/NCT00004931?order=1.

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

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