[Aspirin in primary and secondary prevention of colorectal carcinomas]

Observational but also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. The efficacy appears to be increased with longer duration of treatment, i.e. beyond 5-10 years, but not with increasing doses. Aspirin at 75-100 mg daily appears to be sufficient in both primary as well as secondary prevention of recurrent tumors in sensitive persons, including prevention of distant metastases. The pharmacological mode of aspirin action is unclear as is the question whether only one or more sites of action exist. In any case, the mechanism(s) in charge should work at aspirin plasma levels of 10 microM or less which is the maximum concentration to be expected after antiplatelet doses. Inhibition of COX-1 and/or COX-2 is most likely involved. Follow-up reactions, such as inhibition of platelet-dependent thromboxane formation and action, release of storage products such as VEGF or sphingosine-1-phosphate and acetylation of COX-2 with subsequent generation of antioncogenic lipid mediators, such as lipoxins, are also possible. There is not much likelihood for "direct" actions of aspirin, shown in vitro at concentrations of 5 mM and more, which uncouple oxidative phosphorylation and paralyse the cell energy metabolism. benefit/risk profile, specifically regarding severe or fatal bleedings (GI-tract, cerebral). Accordingly, the actual German guideline "colorectal carcinoma" does not recommend aspirin use for prophylactic purposes. What is strongly needed are definitions of risk patients in terms of biomarkers or genetic profiling as well as data from long-term prospective randomized trials--both are underway.