Racial disparities in patient outcome for colorectal cancer (CRC) have been described in the literature. Various reasons have been implicated as factors related to the disparity. For example, patients of lower socioeconomic status may not be able to access regular care, cancer screening or treatment.1 In particular, minority patients have a higher incidence and death rate from some cancers compared to white patients in the United States.2 For CRC, black patients frequently present with more advanced disease which can negatively affect outcome.1,3-4 CRC may occur at a younger age in black patients, which might affect outcome as well. Additionally, genetic differences in drug metabolism may affect drug efficacy and tolerability. There is little existing data available on response and toxicity of chemotherapy regimens among different racial groups, including the black population of patients with CRC.1 Two recent papers discuss the possible reasons for the different outcomes.
First Study
Sanoff and colleagues1 recently reported on racial differences in advanced CRC outcomes in a subgroup analysis of a large randomized clinical trial. Study facts include:
- An examination of adverse events (AEs), response rate (RR), time to progression (TTP), overall survival (OS), and dose-intensity in 1,412 patients
- The patients were all treated with irinotecan/fluorouracil (IFL), fluorouracil/oxaliplatin (FOLFOX), or irinotecan/oxaliplatin (IROX)
- Pharmacogenetic analysis was performed on 486 patients with blood available for germline DNA analysis
The study results showed that there was suggestive evidence that the effect of the treatment arm on OS varied by race, although statistically the OS was not significantly different.
Black White
|
Adverse events (grade 3 or higher) |
34% |
48% (P = .004) |
|
Overall survival |
16.3 months |
17.8 months (P = .28) |
When broken down into specific treatment types, the results showed that:
Overall Survival Black White
|
IFL |
12.2 (months) |
15.2 (months) P = .02 |
|
FOLFOX |
16.6 (months) |
19.1 (months) P = .23 |
|
IROX |
22.1 (months) |
16.8 (months) P = .15 |
Time to Progression Black White
|
IFL |
5.5 (months) |
6.8 (months) P = .11 |
|
FOLFOX |
11.0 (months) |
9.2 (months) P = .21 |
|
IROX |
7.3 (months) |
6.9 (months) P = .20 |
Response Rate Black White
|
IFL |
28.2% |
32.8% P = .56 |
|
FOLFOX |
28.6% |
48.0% P = .008 |
|
IROX |
28.0% |
37.5% P = .31 |
Although a statistically significant three months shorter survival time was noted with black patients versus white patients in the IFL regimen, the difference was not as significant in the current standard regimen of FOLFOX.
A number of significant associations between race and genotype of drug-metabolizing enzymes were noted. The small sample size did not allow definitive conclusions about the true association between drug toxicity and tumor response by race.1
- The lower RR in the black patients may have occurred because of pharmacogenetic differences with those patients having lower drug exposure even with equal dose-intensity
- The white patients had an absolute 12% higher rate of severe diarrhea versus the black patients (23% vs 8% respectively, P = < .001)
- Further study of the lower rates of AEs reported by black patients might support dose-escalation trials to improve the RR
However the authors conclude that determination of objective predictors of treatment response, such as genotype, would be a better strategy than dose-escalation. Furthermore, examination of the roles between toxicity, race and genotype will help to identify a complex of genes that may point to the reason for racial discrepancy in both response and severe diarrhea, further helping to individualize therapy for patients with CRC.
Second Study
Yan and colleagues5 examined racial differences in CRC survival in the Detroit Metropolitan area in 9,078 patients with primary invasive CRC between 1988 and 1992 (using SEER data). The authors found that African Americans were
- More likely to be diagnosed with stage IV disease (P < .001)
- Live in poorer areas of the city (P < .001)
- Had a significantly higher risk of death as compared to white patients
However, once the data were adjusted for age, marital status, sex, socioeconomic status (SES) group, TNM and treatment, race was no longer significantly associated with OS (HR, 1.00; 95% CI, 0.92-1.09). The authors concluded that although the initial review of the data showed a racial disparity, once the data was adjusted for other factors, this disparity was no longer present.
Summary
The previous studies attempt to address the differences between patient outcome and survival in colorectal cancer with regard to race. Further study is needed to definitively show racial differences and survival with CRC as well as identification of genes that may outline the reason for possible differences in outcome, aiding clinicians in true individualized therapy.
References
- Sanoff HK, Sargent DJ, Green EM, et al. Racial differences in advanced colorectal cancer and pharmcogenetics: A subgroup analysis of a randomized clinical trial. J Clin Oncol, 2009;27, published ahead of print. Abstract may be accessed at: http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.21.9527v1
- Polite BN, Dignam JJ, Olopade OI. Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites. Med Clin North Am. 2005;89:771-793. Abstract may be viewed at: http://www.ncbi.nlm.nih.gov/pubmed/15925649?ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum.
- Alexander DD, Waterbor J, Hughes T, et al. African-American and Caucasian disparities in colorectal cancer mortality and survival by data source: an epidemiologic review. Cancer Biomark. 2007;3:301-13. Free full text article may be viewed at: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2667694&blobtype=pdf
- Chien C, Morimoto LM, Tom J, et al. Differences in colorectal stage and survival by race and ethnicity. Cancer. 2005;104:629-639. Full free text is available at:
http://www3.interscience.wiley.com/cgi-bin/fulltext/110529840/PDFSTART
- Yan B, Noone AM, Yee C, et al. Racial differences in colorectal cancer survival in the Detroit Metropolitan area. Cancer. 2009;115:3791-3800. Abstract may be viewed at: http://www3.interscience.wiley.com/journal/122511186/abstract