Evaluating Intermittent Dosing of Aspirin for Colorectal Cancer Chemoprevention
Mené sur 81 personnes, cet essai randomisé de phase II compare l'efficacité, du point de vue de la modulation des biomarqueurs du risque de cancer colorectal (rapport Ki-67/bax), de cycles intermittents d'aspirine (325 mg par jour) par rapport à une administration continue
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.