Originally published as JCO Early Release 10.1200/JCO.2009.21.9527 on July 27 2009

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Racial Differences in Advanced Colorectal Cancer Outcomes and Pharmacogenetics: A Subgroup Analysis of a Large Randomized Clinical Trial

From the Department of Medicine, Division of Hematology/Oncology; the Lineberger Comprehensive Cancer Center; and the University of North Carolina Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC; and Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.

Corresponding author: Richard Goldberg, MD, University of North Carolina Hematology-Oncology, CB 7305, 3rd Floor, Physician's Office Bldg, 170 Manning Dr, Chapel Hill, NC 27599-7305; e-mail: goldberg{at}med.unc.edu.

Purpose Racial disparities in colorectal cancer (CRC) survival are documented, but there are few data on comparative response to chemotherapy. A subgroup analysis of a multisite National Cancer Institute–sponsored trial (N9741) was performed comparing outcomes of black and white patients with metastatic CRC receiving uniform treatment.

Patients and Methods Adverse events (AEs), response rate (RR), time to progression (TTP), overall survival (OS), and dose-intensity were examined as a function of self-reported race in 1,412 patients treated with irinotecan/fluorouracil, fluorouracil/oxaliplatin, or irinotecan/oxaliplatin. Pharmacogenetic analysis was performed on 486 patients with blood available for germline DNA analysis.

Results OS was 1.5 months shorter and TTP was 0.6 months shorter in black than white patients (OS: hazard ratio [HR] = 1.13; 95% CI, 0.90 to 1.42; TTP: HR = 0.91, 95% CI, 0.73 to 1.13); neither difference was statistically significant. RR was significantly higher in whites (41%) than blacks (28%; P = .008). Grade 3 or greater AEs were also higher in whites (48%) than blacks (34%; P = .004). These relationships were maintained in multivariate models adjusting for arm, age, sex, and performance status. There was no difference in dose-intensity of delivered therapy. Significant racial differences in prevalence of pharmacogenetic variants were observed, although small sample size precluded investigating the relationship between treatment, race, and genotype.

Conclusion OS and TTP are similar in black and white patients treated per protocol with standardized therapy for metastatic CRC. However, RR and AEs vary considerably by race. The marked racial differences in relevant pharmacogenetics, a potential explanation for differing RR and AEs, are worthy of future study.

Supported by National Institutes of Health Grants No. CA25224, CA32102, CA38926, CA21115, CA77202, and KL2 RR025746 (H.K.S.); Pfizer Oncology; and sanofi-aventis.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

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

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				R. M. Goldberg, D. J. Sargent, R. F. Morton, E. Green, H. K. Sanoff, H. McLeod, and J. Buckner NCCTG Study N9741: Leveraging Learning from an NCI Cooperative Group Phase III Trial Oncologist, October 1, 2009; 14(10): 970 - 978. [Abstract] [Full Text] [PDF]