title: Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence.
abstract: 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.
authors.affiliation: Department of Medicine, Arizona Cancer Center, College of Public Health, University of Arizona, Tucson, AZ, USA. dalberts@azcc.arizona.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: María Elena
authors.initials: ME
authors.lastname: Martínez
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hess
authors.forename: Janine G
authors.initials: JG
authors.lastname: Einspahr
authors.forename: Sylvan B
authors.initials: SB
authors.lastname: Green
authors.forename: A K
authors.initials: AK
authors.lastname: Bhattacharyya
authors.forename: Jose
authors.initials: J
authors.lastname: Guillen
authors.forename: Mary
authors.initials: M
authors.lastname: Krutzsch
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Batta
authors.forename: Gerald
authors.initials: G
authors.lastname: Salen
authors.forename: Liane
authors.initials: L
authors.lastname: Fales
authors.forename: Kris
authors.initials: K
authors.lastname: Koonce
authors.forename: Dianne
authors.initials: D
authors.lastname: Parish
authors.forename: Mary
authors.initials: M
authors.lastname: Clouser
authors.forename: Denise
authors.initials: D
authors.lastname: Roe
authors.forename: Peter
authors.initials: P
authors.lastname: Lance
mesh_terms: D000236:Adenoma / Q000473:pathology / Q000517:prevention & control*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014580:Ursodeoxycholic Acid