The optimal dose of Aspirin as an adjuvant agent for
colorectal cancer is not known. There have been, to date,
no randomised Aspirin trials exploring secondary prevention
as an endpoint. Non-randomised studies evaluating
Aspirin as a primary prevention agent have suggested that
a dose of 325 mg a day for 5 years is effective [32]. In the
analysis of the Nurses Health Study, regular use of standard
Aspirin (325 mg) twice or more per week was shown
to reduce the incidence of colorectal cancers. In contrast,
analysis from randomised cardiovascular and stroke trials
did not support additional benefit above 75 mg [45]. In
the polyp prevention study by Baron et al, a lower dose
(81 mg) of Aspirin appeared to be at least equally as effective
as an intermediate dose (325 mg) in preventing recurrence
of polyps [46]. In addition, dose escalation studies in
normal human subjects using mucosal PGE2 as a biomarker
have suggested that 81 mg Aspirin dose was sufficient
to significantly suppress rectal mucosal PGE2 levels and
did so to an equivalent extent as higher doses [47,48]. Our
study using a 200 mg daily dose, falling into the middle of
the range of doses in earlier studies - reflects the ongoing
uncertainty concerning optimal dose. Whilst recognizing
that standard dose Aspirin (i.e. 325 mg OD) may be the
most logical dose to pursue in this clinical trial, we feel
that a 200 mg intermediate dose would be more tolerable
in our predominantly Asian trial population.