Men and women with colorectal cancer and began regular use of Acetylsalicylic acid ( Aspirin ) had a lower risk of overall and colorectal cancer death compared to patients not using Acetylsalicylic acid.

Numerous prospective, observational studies demonstrate that regular Acetylsalicylic acid use is associated with a lower risk of colorectal adenoma ( a benign tumor ) or cancer.
Acetylsalicylic acid is likely, at least in part, to prevent colorectal neoplasia through inhibition of cyclooxygenase-2 ( COX-2; an enzyme ), which promotes inflammation and cell proliferation, and is overexpressed in the majority of human colorectal tumors.
However, the influence of Acetylsalicylic acid on survival after diagnosis of colorectal cancer has been unknown.

Andrew T. Chan, of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues studied the association between Aspirin use and survival among 1,279 men and women with nonmetastatic ( stage I, II, and III ) colorectal cancer who were participating in 2 large prospective cohort studies ( Nurses' Health Study [NHS] and the Health Professionals Follow-up Study [HPFS] ) that were initiated ( in 1980 and 1986, respectively ) prior to tumor diagnosis and followed up through June 1, 2008.

Within these cohorts, Researchers previously have demonstrated that regular Acetylsalicylic acid use was associated with a reduction in the subsequent risk of developing an initial primary colorectal cancer, particularly tumors with COX-2 overexpression. Because these participants have provided biennially updated data on Acetylsalicylic acid use, we had a unique opportunity to extend these findings by examining the influence of prediagnosis and postdiagnosis Acetylsalicylic acid use on the survival of patients with established colorectal cancer.

For participants who were alive through the end of follow-up, the median time of follow-up from date of diagnosis was 11.8 years. There were 193 total deaths ( 35 percent ) and 81 colorectal cancer-specific deaths ( 15 percent ) among 549 participants who regularly used Acetylsalicylic acid after colorectal cancer diagnosis, compared with 287 ( 39 percent ) total and 141 ( 19 percent ) colorectal cancer-specific deaths among 730 participants who did not use Acetylsalicylic acid. For the entire cohort, the overall 5-year survival was 88 percent for participants who used aspirin compared with 83 percent for those who did not. The corresponding 10-year survival rates were 74 percent and 69 percent.

Regular use of Acetylsalicylic acid after diagnosis was associated with a significant reduction in risk of colorectal cancer-specific death and a reduction in overall mortality. Compared with nonusers, regular Aspirin use after diagnosis was associated with a 29 percent lower risk for colorectal-specific mortality and a 21 percent lower risk for overall mortality. Because the prognosis among stage I participants is generally favorable, the Researchers also examined the influence of Acetylsalicylic acid use among those diagnosed with stage II or III disease and observed similar results.

Among the 719 participants who did not use Acetylsalicylic acid before diagnosis, initiation of use postdiagnosis was associated with a 47 percent lower risk for colorectal cancer-specific mortality and a 32 percent lower risk of overall mortality. In contrast, among participants who were using Acetylsalicylic acid before diagnosis, continuation of Aspirin use postdiagnosis was not associated with a significant reduction in colorectal cancer-specific survival or overall survival.

Among participants with COX-2–positive tumors, regular Acetylsalicylic acid use after diagnosis was associated with a 61 percent lower risk of colorectal cancer-specific death and 38 percent lower risk of overall mortality, whereas postdiagnosis aspirin use was not associated with lower risk of either colorectal cancer-specific or overall mortality for those with COX-2–negative tumors.
This supports the hypothesis that COX-2–positive tumors may be relatively sensitive to the anticancer effect of Acetylsalicylic acid, whereas COX-2–negative tumors may be relatively Acetylsalicylic acid-resistant. Moreover, it potentially explains the observation that the benefit of postdiagnosis Aspirin use on patient survival was not apparent among patients who used Acetylsalicylic acid prior to cancer diagnosis.

These results suggest that Acetylsalicylic acid may influence the biology of established colorectal tumors in addition to preventing their occurrence. The data also highlight the potential for using COX-2 or related markers to tailor Aspirin use among patients with newly diagnosed colorectal cancer. Nonetheless, because the data are observational, routine use of Aspirin or related agents as cancer therapy cannot be recommended, especially in light of concerns over their related toxicities, such as gastrointestinal bleeding. Further studies among patients with colorectal cancer, including placebo-controlled trials of Acetylsalicylic acid or related agents as adjuncts to other routine therapies, are required.

Source: Journal of American Medical Association, 2009

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