Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial

TY - JOUR

T1 - Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial

AU - Pommergaard, Hans Christian

AU - Burcharth, Jakob

AU - Rosenberg, Jacob

AU - Raskov, Hans

N1 - Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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. Methods 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. Results 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. Conclusions 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.

AB - 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. Methods 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. Results 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. Conclusions 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.

KW - Adenoma

KW - Adult

KW - Aged

KW - Aspirin

KW - Calcitriol

KW - Calcium

KW - Chemoprevention

KW - Colectomy

KW - Colorectal Neoplasms

KW - Double-Blind Method

KW - Drug Therapy, Combination

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Prognosis

KW - Prospective Studies

KW - Risk Assessment

KW - Secondary Prevention

KW - Survival Rate

KW - Treatment Outcome

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1053/j.gastro.2015.09.010

DO - 10.1053/j.gastro.2015.09.010

M3 - Journal article

C2 - 26404953

SN - 0016-5085

VL - 150

SP - 114-122.e4

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -