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Research Articles |
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
Cancer Prevention Research 2008 1: 9-11.
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