Originally published as JCO Early Release 10.1200/JCO.2008.17.7147 on November 10 2008

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Five-Year Data and Prognostic Factor Analysis of Oxaliplatin and Irinotecan Combinations for Advanced Colorectal Cancer: N9741

Hanna K. Sanoff, Daniel J. Sargent, Megan E. Campbell, Roscoe F. Morton, Charles S. Fuchs, Ramesh K. Ramanathan, Stephen K. Williamson, Brian P. Findlay, Henry C. Pitot, Richard M. Goldberg

From the Department of Medicine, Division of Hematology/Oncology; and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; Division of Biostatistics, Mayo Clinic, Rochester, MN; Community Clinical Oncology Program, IA Oncology Research Association, Des Moines, IA; Dana-Farber Cancer Institute, Boston, MA; University of Pittsburgh, Pittsburgh, PA; University of Kansas Medical Center, Kansas City, KS; National Cancer Institute of Canada, Saint Catharines, Ontario, Canada

Corresponding author: Richard Goldberg, MD, University of North Carolina at Chapel Hill, Hematology-Oncology, 3009 Old Clinic Building, CB 7305, Chapel Hill, NC 27599-7305; e-mail: goldberg{at}med.unc.edu

Purpose In this report, we update survival (OS) and time-to-progression (TTP) data for the Intergroup trial N9741 after a median 5 years of follow-up by using risk-stratified and prognostic factor analyses to determine if treatment outcomes differ in specific patient subgroups.

Patients and Methods A total of 1,691 patients were randomly assigned to one of seven fluorouracil-, oxaliplatin-, and irinotecan-containing regimens. OS and TTP were calculated by treatment arm and baseline risk group (on the basis of WBC, performance status, number of sites of disease, and alkaline phosphatase). Multivariate prognostic factor analysis was used to assess clinical factors for their relationships to OS, TTP, response, and toxicity by using Cox and logistic regression models.

Results The observed 5-year survival with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) of 9.8% was better than with irinotecan plus bolus fluorouracil and leucovorin (IFL; 3.7%; P = .04) or with bolus irinotecan/oxaliplatin (IROX; 5.1%; P = .128). OS and TTP were significantly longer for FOLFOX (20.2 months and 8.9 months, respectively) than for IFL (14.6 months and 6.1 months, respectively; P < .001 for both) or for IROX (17.3 months and 6.7 months, respectively; P < .001 for both). OS differed by risk group: 20.7 months for low risk, 17.4 months for intermediate risk, and 9.4 months for high risk (P < .001). FOLFOX treatment was superior in all risk groups and was the most powerful prognostic factor for OS, TTP, response rate, and toxicity.

Conclusion The 9.8% 5-year OS in patients with metastatic colorectal cancer who were treated with first-line FOLFOX sets a new benchmark. Neither baseline risk group nor any prognostic factor examined was predictive of treatment-specific outcome. However, treatment efficacy and patient longevity varied as a function of risk group.

published online ahead of print at www.jco.org on November 10, 2008.

Supported by National Institutes of Health Grants No. CA25224, CA32102, CA38926, CA21115, and CA77202; and by Pfizer Oncology and Sanofi-Aventis.

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

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