Aspirin, NSAIDs and colorectal cancer--what do the epidemiological studies show and what do they tell us about the modus operandi?
A large number of observational epidemiological studies show that regular use of aspirin and other NSAID's is associated with a reduction in the risk of developing both colorectal adenomas and cancer. Furthermore, the prodrug sulindac appears clinically to be able to reduce and reverse the growth of existing polyps in familial adenomatous polyposis (FAP). For aspirin and NSAID's the dose, duration of effect and length of protection seen after cessation remain to be fully established. The available data for aspirin suggest that doses higher than those needed for heart disease prevention are required. It is also likely that the drug needs to be taken continuously for a number of years. With regards to randomised controlled trials to evaluate chemopreventive strategies there are so far only limited data available. The only trial reported to date found no effect but employed a relatively low dose of 325 mg of aspirin every other day and the randomised intervention period was relatively short (5 years). Further trials of intermediate endpoints (adenomas) are currently underway in the UK and USA and are employing higher doses of aspirin. Randomised clinical studies of sulindac have been more encouraging demonstrating that it is a useful drug for therapeutic applications in FAP patients. Its relatively greater side effects, however, prevent its consideration for primary chemoprevention. The mechanisms by which NSAID's act are still sought. Strategies for possible primary and secondary chemoprevention in humans also require evaluation.
Muir
K R
KR
Division of Public Health Medicine & Epidemiology, Queens Medical Centre, Nottingham, NG7 2UH, UK.
Logan
R F
RF