Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial - PubMed (original) (raw)

Randomized Controlled Trial

doi: 10.1158/1940-6207.CAPR-08-0042.

Christine E McLaren, Daniel Pelot, Sharon Fujikawa-Brooks, Philip M Carpenter, Ernest Hawk, Gary Kelloff, Michael J Lawson, Jayashri Kidao, John McCracken, C Gregory Albers, Dennis J Ahnen, D Kim Turgeon, Steven Goldschmid, Peter Lance, Curt H Hagedorn, Daniel L Gillen, Eugene W Gerner

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Randomized Controlled Trial

Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial

Frank L Meyskens Jr et al. Cancer Prev Res (Phila). 2008 Jun.

Abstract

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 (> or =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 > or =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.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

MJ Lawson: Bristol-Myers Squibb Commercial Research Grant, Elan Pharmaceuticals Consultant. The other authors disclosed no potential conflicts of interest.

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