Aspirin as Colorectal Cancer Adjuvant Therapy

Abstract

Men and women who were diagnosed with colorectal cancer and began regular use of aspirin had a lower risk of overall and colorectal-specific cancer mortality compared to patients not using aspirin, according to a study in the August 12, 2009, issue of JAMA. Numerous prospective, observational studies have demonstrated that regular aspirin use is associated with a lower risk of colorectal adenoma or cancer. Data indicate that aspirin is likely, at least in part, to prevent colorectal neoplasia through inhibition of cyclooxygenase-2 (COX-2), which promotes inflammation and cell proliferation, and is overexpressed in the majority of human colorectal cancers. However, the influence of aspirin on survival after a diagnosis of colorectal cancer has remained unknown. Andrew T. Chan, MD, MPH, of Massachusetts General Hospital and Harvard Medical School, Boston, and his 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 and the Health Professionals Follow-up Study) that were initiated (in 1980 and 1986, respectively) before cancer diagnosis and followed through June 1, 2008. For participants who were alive through the end of follow-up, the median time of follow-up from the date of diagnosis was 11.8 years. There were 193 total deaths (35%) and 81 colorectal cancer-specific deaths (15%) among 549 participants who regularly used aspirin after a diagnosis of colorectal cancer, compared with 287 (39%) total and 141 (19%) colorectal cancer-specific deaths among 730 participants who did not use aspirin. For the entire cohort, the overall 5-year survival was 88% for participants who used aspirin compared with 83% for those who did not. The corresponding 10-year survival rates were 74% and 69%. Regular aspirin use 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% lower risk for colorectal-specific mortality and a 21% lower risk for overall mortality. Because the prognosis among stage I participants is generally favorable, the researchers also examined the influence of aspirin use among those diagnosed with stage II or III disease and observed similar results. Among the 719 participants who did not use aspirin before diagnosis, initiation postdiagnosis was associated with a 47% lower risk for colorectal cancer-specific mortality and a 32% lower risk of overall mortality. In contrast, among participants who were using aspirin 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 tumors that expressed COX-2, regular aspirin use after diagnosis was associated with a 61% lower risk of colorectal cancer-specific death and a 38% 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 aspirin, whereas COX-2–negative tumors may be relatively aspirin-resistant. Moreover, it potentially explains the observation that the benefit of postdiagnosis aspirin use on patient survival was not apparent among patients who used aspirin prior to cancer diagnosis,” the researchers note. Based on these results, the authors suggest that aspirin may influence the biology of established colorectal tumors in addition to preventing their occurrence. “Our data also highlight the potential for using COX-2 or related markers to tailor aspirin use among patients with newly diagnosed colorectal cancer.”