Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence.
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.
Alberts
David S
DS
Department of Medicine, Arizona Cancer Center, College of Public Health, University of Arizona, Tucson, AZ, USA. dalberts@azcc.arizona.edu
Martínez
María Elena
ME
Hess
Lisa M
LM
Einspahr
Janine G
JG
Green
Sylvan B
SB
Bhattacharyya
A K
AK
Guillen
Jose
J
Krutzsch
Mary
M
Batta
Ashok K
AK
Salen
Gerald
G
Fales
Liane
L
Koonce
Kris
K
Parish
Dianne
D
Clouser
Mary
M
Roe
Denise
D
Lance
Peter
P
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*
D000970:Antineoplastic Agents; D014580:Ursodeoxycholic Acid