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

Frank L. Meyskens, 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, Michael P Lance, Curt H. Hagedorn, Daniel L. Gillen, Eugene W. Gerner

Research output: Contribution to journalArticle

351 Citations (Scopus)

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 (≥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.

Original languageEnglish (US)
Pages (from-to)32-38
Number of pages7
JournalCancer Prevention Research
Volume1
Issue number1
DOIs
StatePublished - Jun 2008

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Sulindac
Eflornithine
Adenoma
Placebos
Colonoscopy
Odds Ratio
Adenomatous Polyps
Recurrence
Chemoprevention
Random Allocation
Aspirin
Hearing
Confidence Intervals
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas : A randomized placebo-controlled, double-blind trial. / Meyskens, Frank L.; McLaren, Christine E.; Pelot, Daniel; Fujikawa-Brooks, Sharon; Carpenter, Philip M.; Hawk, Ernest; Kelloff, Gary; Lawson, Michael J.; Kidao, Jayashri; McCracken, John; Albers, C. Gregory; Ahnen, Dennis J.; Turgeon, D. Kim; Goldschmid, Steven; Lance, Michael P; Hagedorn, Curt H.; Gillen, Daniel L.; Gerner, Eugene W.

In: Cancer Prevention Research, Vol. 1, No. 1, 06.2008, p. 32-38.

Research output: Contribution to journalArticle

Meyskens, FL, McLaren, CE, Pelot, D, Fujikawa-Brooks, S, Carpenter, PM, Hawk, E, Kelloff, G, Lawson, MJ, Kidao, J, McCracken, J, Albers, CG, Ahnen, DJ, Turgeon, DK, Goldschmid, S, Lance, MP, Hagedorn, CH, Gillen, DL & Gerner, EW 2008, 'Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: A randomized placebo-controlled, double-blind trial', Cancer Prevention Research, vol. 1, no. 1, pp. 32-38. https://doi.org/10.1158/1940-6207.CAPR-08-0042
Meyskens, Frank L. ; McLaren, Christine E. ; Pelot, Daniel ; Fujikawa-Brooks, Sharon ; Carpenter, Philip M. ; Hawk, Ernest ; Kelloff, Gary ; Lawson, Michael J. ; Kidao, Jayashri ; McCracken, John ; Albers, C. Gregory ; Ahnen, Dennis J. ; Turgeon, D. Kim ; Goldschmid, Steven ; Lance, Michael P ; Hagedorn, Curt H. ; Gillen, Daniel L. ; Gerner, Eugene W. / Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas : A randomized placebo-controlled, double-blind trial. In: Cancer Prevention Research. 2008 ; Vol. 1, No. 1. pp. 32-38.
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