Is Less More? An Update on Aspirin for Cancer Prevention in Lynch Syndrome From the Cancer Prevention Programme-CaPP

Aspirin has been used to treat pain and fever for 120 years. Its uses expanded into treating arthritis and prevention of thrombotic events. Its anti-cancer role emerged with observational studies in the 1980's and subsequent cancer review in those treated with aspirin in cardiovascular trials. Two randomised placebo-controlled trials with cancer as an endpoint, the Women's Health Study and CAPP2 provided support. The latter involved 861 carriers of Lynch syndrome (LS) who received either 600 mg aspirin or placebo for 2-4 years. Aspirin recipients subsequently had 50% fewer colorectal cancers. CaPP3 randomised 1866 LS carriers to 600 mg, 300 mg or 100/75 mg daily for 2 years blinded then for 3 years open label. Lynch syndrome cancer and colorectal cancer rate mirrored that in the 600 mg limb of CAPP2. Those on the lowest dose had the fewest cancers in keeping with this being equivalent to 600 mg. The Intention to treat confidence intervals fell within the predefined upper limit of 1.5. A survey of primary care doctors revealed only 62% would agree to prescribe the 600 mg dose regardless of guidance. As a normal dietary component, salicylate is likely to influence multiple pathways. Most interesting is the recent demonstration that low dose aspirin blocks release of thromboxane A2, a product of activated platelets which suppresses T cell function. An international Delphi report has endorsed the daily use of 75-100 mg aspirin in adults with Lynch syndrome prior to old age when adverse effects become a greater concern.