Cancer prevention with aspirin: Randomised trial evidence


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John Burn
Institute of Genetic Medicine and John Mathers (Institute of Ageing and Health), Newcastle University & D Tim Bishop (CRUK genetic Epidemiology, Leeds University) on behalf of the CAPP consortium, Newcastle, UK

Abstract

Observational studies show aspirin reduces colorectal cancer, especially with prolonged use. In 4 adenoma prevention RCTs aspirin at any dose reduced the risk of a colorectal adenoma by an average of 17% and advanced adenomas by 28%.Registry follow-up for a median of 18 years after of 5 vascular RCTs showed treatment with any aspirin dose reduced the 20-year of CRC risk by 24% and CRC-associated mortality by 35%. Meta-analysis of 8 trials with a total of 25,570 patients showed 21% lower risk of death from any cancer.

CAPP1 tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200 adolescent FAP carriers. Aspirin treatment resulted in a non-significant reduction in polyp number and a significant reduction in polyp size among patients treated with aspirin for more than 1 year. CAPP2 RCT used the same interventions in 937 Lynch syndrome patients, the first RCT to have cancer prevention as a primary endpoint. Aspirin did not reduce the risk of colorectal neoplasia in a mean treatment period of 29 months but double blind post intervention follow-up has revealed 48 participants developed 53 CRCs. Per protocol analysis showed a 60% fewer cancers with aspirin (p=0ยท02) apparent from 4 years, with a similar effect on other LS cancers.

CAPP3 will involve a double blind dose inferiority trial comparing 100mg, 300mg or 600mg daily in 3000 gene carriers. We can now recommend aspirin in people at high risk of colorectal cancer.

Aspirin has a wide range of cellular effects potentially relevant to cancer prevention and therapy. Investigation of the effects of aspirin as an adjuvant therapy in colorectal cancer has also demonstrated a beneficial effect on recurrence risk. The planned ADD-Aspirin RCT will investigate this further.

All evidence points towards a clear benefit in terms of cancer prevention by use of regular aspirin. Measures to identify those at highest risk and to personalise aspirin doses using the latest DNA testing technologies will be discussed.