Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention.

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Aspirin reduces colorectal cancer risk but has a potential for adverse effects. Recent pre-clinical data suggest that intermittent dosing of aspirin may minimize adverse effects maintaining efficacy. We conducted a three-arm double-blind randomized placebo-controlled Phase II trial. The primary objective of the study was to test for the equivalency of the two aspirin schedules, i.e., the effects of daily aspirin 325 mg/day continuously (cont-ASA) for 12 weeks or intermittently, 3-weeks on/3-weeks off (int-ASA) on biomarkers related to colorectal carcinogenesis in rectal mucosa. A placebo group enabled the estimation of spontaneous biomarker variation. 81 participants were randomized, of whom 45 were evaluable. For the primary endpoint of decrease in the Ki-67:BAX ratio, we could not establish equivalence for the two treatment regimens, and also found no significant difference between them. For the secondary endpoint, cont-ASA treatment was significantly more effective in reducing Ki-67:TUNEL ratio. Among exploratory endpoints, we found more reduction in epithelial COX-2 expression in cont-ASA arm compared to int-ASA arm. We did not observe significant differences in other secondary and exploratory endpoints. Intermittent aspirin dosing in 3-week cycles does not produce the same biologic effect as continuous dosing. Future studies should examine whether the 1-week on/1-week off schedule can maximize the efficacy and minimize the side effects.