Aspirin cancer-reduction trials would probably be judged unethical

27 Mar 2009

Evidence exists for the protective effects exerted by aspirin on cancer, especially colorectal cancer. However, there would be ethical constraints on conducting randomised controlled trials to gather evidence, and aspirin has side effects such as bleeding. This means that more evidence from all possible sources is needed, and work should be done to create a safer form of aspirin.

The issues are discussed in a Review published Online and in an upcoming edition of The Lancet, written by Professor Peter Elwood, University of Cardiff, UK, and Dr Alison Gallagher, Northern Ireland Centre for Food and Health, University of Ulster, UK, and colleagues.

Aspirin has well documented benefits on vascular disease, but the most conclusive evidence for an association between aspirin and cancer would be shown by randomised controlled trials. However, the risks of vascular events and cancer increase with age, and the denial of vascular benefits to participants in the control group of new cancer-reduction trials would probably be judged unethical.

The development of polyps in the colon or rectum is a precursor to colorectal cancer. Various studies have shown aspirin to reduce the risk of polyps recurring or new polyps forming. Advanced polyps seemed to be affected more by aspirin, suggesting that its effect might increase in the later stages of the polyp changing into fully blown cancer. Regular reports from the US Nurses’ Health Study of some 80,000 women showed a 12% reduction in cancer deaths with aspirin use, which became statistically significant by 10 years and increased to 44% by 20 years.

Randomised studies of chemically induced cancer in animals show that
i) tumour suppression is greatest if aspirin use begins before or at the same time as exposure to the carcinogen;
ii) both selective and non-selective NSAIDs* inhibit tumour development;
iii) prophylaxis should continue without interruption. Plants also provide evidence of the benefits of aspirin, since the active ingredients of aspirin (salicylates) occur naturally in plants and exert a similar protective effect. Many herbs and spices are especially rich in salicylates, which could be of relevance to international differences in cancer incidence.

The dose of aspirin needed to exert a protective effect is not known. Two studies have suggested 81mg daily may be effective, but others have suggested higher doses of 300mg or more could be necessary. Several studies have identified the importance of duration and continuity of use, for example in the Nurse’s Health Study noted above.
The authors conclude by calling for more evidence from every possible source on the effect of aspirin on cancer, and say: “Aspirin is prone to undesirable side-effects, in particular bleeding, and development of a safer form of aspirin, or a drug combination, should be urgently undertaken to improve the risk-benefit balance.
“The risk-benefit balance of aspirin for cancer prophylaxis should be assessed in conjunction with its well-established benefits in vascular disease.”

Professor Elwood adds: “Aspirin is readily available over-the-counter and we must recognise that it is the patient’s own evaluation of the risk and benefits of aspirin that count in the end. Our responsibility is to inform the public of these risks and benefits in as balanced a way as possible.”