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

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.

• Authors: Frank L Meyskens Jr, 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
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 1 Issue 1 Pg. 32-8 (Jun 2008) ISSN: 1940-6215 [Electronic] United States
• PMID: 18841250 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Placebos
• Sulindac
• Eflornithine

Topics

• Adenoma (diagnosis, prevention & control)
• Adult
• Aged
• Algorithms
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Colonoscopy
• Colorectal Neoplasms (diagnosis, prevention & control)
• Double-Blind Method
• Eflornithine (administration & dosage, adverse effects)
• Female
• Humans
• Male
• Middle Aged
• Placebos
• Sulindac (administration & dosage, adverse effects)
• Treatment Outcome