BACKGROUND & AIMS:
Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal adenoma recurrence.
We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010. Inclusion criteria were 1 adenoma greater than 1 cm in diameter, more than 1 adenoma of any size, or an adenoma of any size and first-degree relatives with colorectal cancer. Subjects were assigned randomly to groups given 0.5 μg calcitriol, 75 mg acetylsalicylic acid, and 1250 mg calcium carbonate (n = 209), or placebo (n = 218), each day for 3 years. The primary outcome was adenoma recurrence assessed by colonoscopy after 3 years. Secondary outcomes were the proportion of patients with advanced adenomas, the total number of colorectal adenomas, and adenoma size and features.
The trial was stopped in October 2010 because of futility. In this analysis, we found no differences between groups in the rate of recurrence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.61-1.48), adverse effects, or secondary outcomes. Subgroup analyses indicated that the treatment effects may be influenced by smoking status (nonsmokers OR, 0.65; 95% CI, 0.26-1.22 vs current smokers OR, 1.70; 95% CI, 0.70-4.09; P value interaction < .05). However, the overall interaction was not significant.
In a prospective study, the combination of calcitriol, aspirin, and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period. The negative results might be owing to the effects of smoking or low doses of the tested agents. Clinicaltrials.gov number: NCT00486512.