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not those of the American Medical Association.
Aspirin as Adjuvant Therapy
for Colorectal Cancer
A Promising New Twist for an Old Drug
greater among patients who initiated aspirin use aftercancer diagnosis than among those who used it before, and the benefit was limited to those with tumors that VEN BEFORE THE TIME OF HIPPOCRATES, WILLOW EX-tracts, which contain salicylates, were used in medi- cine as analgesic, anti-inflammatory, and antipy- Although these findings are based on an observational retic agents. Acetylsalicylic acid was isolated in the study rather than an intervention trial, they meet many of mid-19th century, and since 1899 when it was patented, as- the usual criteria for acceptance as valid and causal. In a pirin has enjoyed global popularity. The relatively recent previous observational study of stage III colon cancer discovery of its antiplatelet activity has also led to the wide- patients treated in a randomized chemotherapy trial, spread use of aspirin as an antistroke and cardioprotective Fuchs et al12 found similar survival benefits among con- agent, but the list of its medical applications continues to sistent aspirin users. The finding that former aspirin users derived less benefit from subsequent aspirin use More than 30 years ago, Sporn et al2 coined the term than former nonusers did is biologically plausible, con- chemoprevention to describe and propose the use of oral sidering the tumors that developed in former users were drugs, chemicals, or supplements to reduce the risk of can- not prevented by aspirin use. Furthermore, the results cer. In the ensuing decades, chemoprevention research has were consistent across a variety of strata such as age, sex, generated high hopes and enormous increases in funding, and cancer site (colon vs rectum). Most compelling, the although only a few agents have shown efficacy in clinical benefits of aspirin use were observed only among patients trials, and of those few, most are too toxic for use by who had COX-2–expressing tumors, enhancing the bio- average-risk individuals. In addition to its other effects, logical plausibility of the findings.
aspirin has been shown to be a potentially effective chemo- In the study by Chan et al,11 the survival benefits of aspi- preventive agent for a number of cancers, but most clearly rin were similar in patients who received standard adju- for colorectal neoplasia.3 Numerous observational studies vant chemotherapy and those who did not, and in patients and randomized trials have demonstrated the efficacy of with stage I and stage II disease as well as those who had aspirin against the development of colorectal adenomas stage III disease at diagnosis. Thus, aspirin may have the and cancer through its actions as an inhibitor of the potential to be useful as adjuvant therapy not just for cyclooxygenase 2 (COX-2) pathway, which is overex- locally advanced disease but for early stage patients as pressed in 80% to 85% of colorectal cancers.4,5 Nonethe- well. Further studies are needed to confirm and extend less, aspirin is not recommended as a colorectal cancer these findings, and should also investigate the use of aspi- chemopreventive agent because of its adverse effects— rin as an agent in individuals with metastatic disease. One notably gastrointestinal irritation and bleeding.6 Specific such study is the Bolus, Infusional, or Capecitabine with COX-2 inhibitors, such as rofecoxib or celecoxib, which Camptosar-Celecoxib (BICC-C) study, which started in have less gastrointestinal toxicity than aspirin, also have 2003 and randomized patients with untreated metastatic failed to come into widespread use because of their unex- colorectal cancer to 1 of 3 chemotherapy regimens, and in addition randomized them to either a COX-2 inhibitor However, aspirin may now have yet another new role (celecoxib) or placebo.13 The COX-2 inhibitor portion of as a cancer treatment agent, at least in the adjuvant set- the study was discontinued in 2005 because the cardiovas- ting. In this issue of JAMA, Chan and colleagues11 report cular toxicity of the agent became apparent14 and initial that, among patients with colorectal cancer participating results of the trial indicated no survival benefit for the in a large cohort study, aspirin users had a 29% lower cancer-specific mortality and a 21% lower overall mortal- Author Affiliations: Department of Medicine and Herbert Irving Comprehensive
ity than nonusers. The reduction in mortality was even Cancer Center, College of Physicians and Surgeons, and the Department of Epi-demiology, Mailman School of Public Health, Columbia University, New York, NewYork.
See also p 649.
Corresponding Author: Alfred I. Neugut, MD, PhD, Columbia University Medical
Center, 630 W 168th St, New York, NY 10032 (
688 JAMA, August 12, 2009—Vol 302, No. 6 (Reprinted)
2009 American Medical Association. All rights reserved.
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Financial Disclosures: None reported.
tergroup trial CALGB 89803. J Clin Oncol. 2008;26(15s):4039.
2009 American Medical Association. All rights reserved.
(Reprinted) JAMA, August 12, 2009—Vol 302, No. 6 689


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