This Article Full Text Full Text (PDF) Perspective on This Article All Versions of this Article: 1940-6207.CAPR-08-0042v1 1/1/32    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyskens, F. L. Articles by Gerner, E. W. Search for Related Content PubMed PubMed Citation Articles by Meyskens, F. L., Jr. Articles by Gerner, E. W. Related Collections Commentary

Difluoromethylornithine Plus Sulindac for the Prevention of Sporadic Colorectal Adenomas: A Randomized Placebo-Controlled, Double-Blind Trial

Authors' Affiliations: ¹ Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, California; ² Arizona Cancer Center, University of Arizona, Tucson, Arizona; ³ Department of Veterans Affairs Long Beach Healthcare System, Long Beach, California; ⁴ Loma Linda University, Loma Linda, California; ⁵ University of Michigan, Ann Arbor, Michigan; ⁶ Denver Department of Veteran Affairs Medical Center and University of Colorado, Denver, Colorado; ⁷ Kaiser Permanente, Sacramento, California; ⁸ University of Kansas, Kansas City, Kansas; and ⁹ National Cancer Institute, Bethesda, Maryland

Requests for reprints: Frank L. Meyskens, Jr., UCI Cancer Center, Building 44, Route 81, 101 City Drive Cancer Center Orange CA 92668. Phone: 714-456-6310; Fax: 1-714-456-2240; E-mail: flmeyske{at}uci.edu.

Preclinical studies of chemoprevention drugs given in combination at low doses show remarkable efficacy in preventing adenomas with little additional toxicities, suggesting a strategy to improve risk to benefit ratios for preventing recurrent adenomas. Three hundred seventy-five patients with history of resected (3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline and clinical site. Follow-up colonoscopy was done 3 years after randomization or off-study. Colorectal adenoma recurrence was compared among the groups with log-binomial regression. Comparing the outcome in patients receiving placebos to those receiving active intervention, (a) the recurrence of one or more adenomas was 41.1% and 12.3% (risk ratio, 0.30; 95% confidence interval, 0.18-0.49; P < 0.001); (b) 8.5% had one or more advanced adenomas, compared with 0.7% of patients (risk ratio, 0.085; 95% confidence interval, 0.011-0.65; P < 0.001); and (c) 17 (13.2%) patients had multiple adenomas (>1) at the final colonoscopy, compared with 1 (0.7%; risk ratio, 0.055; 0.0074-0.41; P < 0.001). Serious adverse events (grade 3) occurred in 8.2% of patients in the placebo group, compared with 11% in the active intervention group (P = 0.35). There was no significant difference in the proportion of patients reporting hearing changes from baseline. Recurrent adenomatous polyps can be markedly reduced by a combination of low oral doses of DFMO and sulindac and with few side effects.

Commentary

Clinical Prevention of Recurrence of Colorectal Adenomas by the Combination of Difluoromethylornithine and Sulindac: An Important Milestone

Michael B. Sporn and Waun Ki Hong
Cancer Prevention Research 2008 1: 9-11. [Full Text] [PDF]

This article has been cited by other articles:

				N. A. IGNATENKO, H. F. YERUSHALMI, R. PANDEY, K. L. KACHEL, D. E. STRINGER, L. J. MARTON, and E. W. GERNER Gene Expression Analysis of HCT116 Colon Tumor-derived Cells Treated with the Polyamine Analog PG-11047 Cancer Genomics Proteomics, May 1, 2009; 6(3): 161 - 175. [Abstract] [Full Text] [PDF]

				L. J. Marnett Mechanisms of Cyclooxygenase-2 Inhibition and Cardiovascular Side Effects--The Plot Thickens Cancer Prevention Research, April 1, 2009; 2(4): 288 - 290. [Full Text] [PDF]

				J. A. Zell, D. Pelot, W.-P. Chen, C. E. McLaren, E. W. Gerner, and F. L. Meyskens Risk of Cardiovascular Events in a Randomized Placebo-Controlled, Double-Blind Trial of Difluoromethylornithine plus Sulindac for the Prevention of Sporadic Colorectal Adenomas Cancer Prevention Research, March 1, 2009; 2(3): 209 - 212. [Abstract] [Full Text] [PDF]

				M. M. Bertagnolli, A. G. Zauber, and S. Solomon Prostaglandin Inhibition and Cardiovascular Risk: Maybe Timing Really Is Everything Cancer Prevention Research, March 1, 2009; 2(3): 195 - 196. [Full Text] [PDF]

				G. E. Goodman Assessing Toxicity in Cancer Chemoprevention Trials: The Other Side of the Coin Cancer Prevention Research, December 1, 2008; 1(7): 499 - 502. [Full Text] [PDF]

				C. E. McLaren, S. Fujikawa-Brooks, W.-P. Chen, D. L. Gillen, D. Pelot, E. W. Gerner, and F. L. Meyskens Jr. Longitudinal Assessment of Air Conduction Audiograms in a Phase III Clinical Trial of Difluoromethylornithine and Sulindac for Prevention of Sporadic Colorectal Adenomas Cancer Prevention Research, December 1, 2008; 1(7): 514 - 521. [Abstract] [Full Text] [PDF]

				E. Szabo Assessing Efficacy in Early-Phase Cancer Prevention Trials: The Case of Oral Premalignancy Cancer Prevention Research, October 1, 2008; 1(5): 312 - 315. [Full Text] [PDF]