© 2005 Oxford University Press
ARTICLE |
Phase III Trial of Ursodeoxycholic Acid To Prevent Colorectal Adenoma Recurrence
For the Phoenix and Tucson Gastroenterologist Networks
Affiliations of authors: Departments of Medicine (DSA, JGE, PL), Pathology (AKB), and the Arizona Cancer Center (DSA, MEM, LMH, JGE, SBG, AK Bhattacharyya, JG, MK, LF, KK, DP, MC, DR, PL), College of Medicine, Division of Biostatistics and Epidemiology, College of Public Health (DSA, MEM, SBG, DR), and the Department of Molecular and Cellular Biology, College of Science (PL), University of Arizona, Tucson; Department of Medicine (AK Batta, GS), University of Medicine and Dentistry of New Jersey, Newark
Correspondence to: David S. Alberts, MD, Arizona Cancer Center, 1515 N. Campbell Avenue, PO Box 245024, Tucson, AZ 85724–5024 (e-mail: dalberts{at}azcc.arizona.edu).
Background: Ursodeoxycholic acid (UDCA) treatment is associated with a reduced incidence of colonic neoplasia in preclinical models and in patients with conditions associated with an increased risk for colon cancer. We conducted a phase III, double-blind placebo-controlled trial of UDCA to evaluate its ability to prevent colorectal adenoma recurrence. Methods: We randomly assigned 1285 individuals who had undergone removal of a colorectal adenoma within the past 6 months to daily treatment with UDCA (8–10 mg/kg of body weight; 661 participants) or with placebo (624 participants) for 3 years or until follow-up colonoscopy. Recurrence rates (number of recurrent adenomas per unit time) were compared by use of a Huber–White variance estimator. Proportions of participants with one or more recurrent adenomas were compared with a Pearson chi-square statistic; adjusted odds ratios (ORs) were obtained by logistic regression. All statistical tests were two-sided. Results: We observed a non–statistically significant 12% reduction in the adenoma recurrence rate associated with UDCA treatment, compared with placebo treatment. However, UDCA treatment was associated with a statistically significant reduction (P = .03) in the recurrence of adenomas with high-grade dysplasia (adjusted OR = 0.61, 95% confidence interval = 0.39 to 0.96). We observed no statistically significant differences between UDCA and placebo groups in recurrence with regard to adenoma size, villous histology, or location. Conclusions: UDCA treatment was associated with a non–statistically significant reduction in total colorectal adenoma recurrence but with a statistically significant 39% reduction in recurrence of adenomas with high-grade dysplasia. Because severely dysplastic lesions have a high risk of progression to invasive colorectal carcinoma, this finding indicates that future chemoprevention trials of UDCA in individuals with such lesions should be considered.
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