Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence

David S Alberts, María Elena Martínez, Lisa M. Hess, Janine G Einspahr, Sylvan B. Green, Achyut K Bhattacharyya, Jose Guillen, Mary Krutzsch, Ashok K. Batta, Gerald Salen, Liane Fales, Kris Koonce, Dianne Parish, Mary Clouser, Denise Roe, Michael P Lance

Research output: Contribution to journalArticle

171 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)846-853
Number of pages8
JournalJournal of the National Cancer Institute
Volume97
Issue number11
DOIs
StatePublished - Jun 1 2005

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Ursodeoxycholic Acid
Adenoma
Recurrence
Placebos
Therapeutics
Odds Ratio
Villous Adenoma
Chemoprevention
Colonoscopy
Colonic Neoplasms
Colorectal Neoplasms
Histology
Logistic Models
Body Weight
Confidence Intervals

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. / Alberts, David S; Martínez, María Elena; Hess, Lisa M.; Einspahr, Janine G; Green, Sylvan B.; Bhattacharyya, Achyut K; Guillen, Jose; Krutzsch, Mary; Batta, Ashok K.; Salen, Gerald; Fales, Liane; Koonce, Kris; Parish, Dianne; Clouser, Mary; Roe, Denise; Lance, Michael P.

In: Journal of the National Cancer Institute, Vol. 97, No. 11, 01.06.2005, p. 846-853.

Research output: Contribution to journalArticle

Alberts, DS, Martínez, ME, Hess, LM, Einspahr, JG, Green, SB, Bhattacharyya, AK, Guillen, J, Krutzsch, M, Batta, AK, Salen, G, Fales, L, Koonce, K, Parish, D, Clouser, M, Roe, D & Lance, MP 2005, 'Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence', Journal of the National Cancer Institute, vol. 97, no. 11, pp. 846-853. https://doi.org/10.1093/jnci/dji144
Alberts, David S ; Martínez, María Elena ; Hess, Lisa M. ; Einspahr, Janine G ; Green, Sylvan B. ; Bhattacharyya, Achyut K ; Guillen, Jose ; Krutzsch, Mary ; Batta, Ashok K. ; Salen, Gerald ; Fales, Liane ; Koonce, Kris ; Parish, Dianne ; Clouser, Mary ; Roe, Denise ; Lance, Michael P. / Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. In: Journal of the National Cancer Institute. 2005 ; Vol. 97, No. 11. pp. 846-853.
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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.",
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T1 - Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence

AU - Alberts, David S

AU - Martínez, María Elena

AU - Hess, Lisa M.

AU - Einspahr, Janine G

AU - Green, Sylvan B.

AU - Bhattacharyya, Achyut K

AU - Guillen, Jose

AU - Krutzsch, Mary

AU - Batta, Ashok K.

AU - Salen, Gerald

AU - Fales, Liane

AU - Koonce, Kris

AU - Parish, Dianne

AU - Clouser, Mary

AU - Roe, Denise

AU - Lance, Michael P

PY - 2005/6/1

Y1 - 2005/6/1

N2 - 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.

AB - 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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