Saturday, April 18, 2015

Aspirin As An Anti-Cancer Agent

Aspirin As An Anti-Cancer Agent

Aspirin [acetylsalicylic acid, ASA] is used as an analgesic, antipyretic and as an anti-inflammatory medication. Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels. The platelet patch can become too large and also block blood flow, locally and downstream, aspirin is also used long-term, at low doses, to help prevent heart attacks, strokes, and blood clot formation in people at high risk of developing blood clots.

Aspirin

The role of aspirin in chemoprevention was first provided in a case-control study in 1988, where an odds ratio (OR) of 0.53 for Colorectal Cancer (CRC) incidence was observed for chronic users of aspirin compared with nonusers [1]. In response to these studies, randomised trials were designed to evaluate the role of aspirin in preventing cancer. Two of the studies determined the incidence of CRC in large healthy populations and were unable to demonstrate a chemopreventive effect for aspirin [2].

Since 2012 onwards, more and more reports are being published where aspirin is being projected as a fighter drug against certain types of cancer, particularly colorectal cancer [1]. The mechanism is still unknown, but a report suggest that aspirin reduces the overall risk of both getting cancer and dying from cancer. The finding suggests that aspirin might help in treatment of some cancers and provides proof of principle for pharmacological intervention specifically to prevent distant metastasis [3].

The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period [4].

Daily aspirin use has been convincingly shown to reduce the risk of colorectal cancer and recurrence of adenomatous polyps, but in average-risk populations, these benefits alone do not outweigh harms from aspirin-induced bleeding [5].


In order to understand the wide usuage of aspirin, the researchers designed a study to assess patients’ knowledge of aspirin and identify factors contributing to regular use. A survey of U.S. adults aged 45-75 years was performed to ascertain aspirin use and factors that may be associated with use. Multivariate logistic regression was used to identify predictors of current use of aspirin among those with a primary prevention indication. The results showed a link between aspirin and a 34 percent reduction in deaths from all cancers and a 54 percent reduction in gastrointestinal cancer. There were also benefits in terms of oesophageal, lung pancreatic and prostate cancers [6].

Studies linking aspirin in reduction of death from cancers are reported, but in absence of any concrete mechanism, it is just too early to say anything. We all hope that these researches are true, because we all need affordable drug molecules.

References:
1. Kune G. A.; et. al. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res 1988, 48(15), 4399-4404.
2. Manzano, A.; et. al. Colorectal cancer chemoprevention: is this the future of colorectal cancer prevention? ScientificWorldJournal 2012, 2012:327341.
3.Rothwell, P. M.; et. al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012, 379(9826), 1591-1601.
4. Cuzick, J.; et. al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2015, 26(1), 47-57.
5. Thun, M. J.; et. al. The role of aspirin in cancer prevention. Nat Rev Clin Oncol 2012, 9(5), 259-267.
6. Williams, C. D.; et. al. Aspirin Use Among Adults in the U.S. Am J Prev Med 2015, 48(5), 501-508.