Rationale for, and design of, a clinical trial targeting polyamine metabolism for colon cancer chemoprevention

E. W. Gerner, F. L. Meyskens, S. Goldschmid, P. Lance, D. Pelot

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations


Polyamine metabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers. Inhibitors of ornithine decarboxylase, such as difluoromethylornithine (DFMO), and agents that stimulate polyamine acetylation and export, such as non-steroidal anti-inflammatory drugs (NSAIDS), act at least additively to arrest growth in human cell models and suppress intestinal carcinogenesis in mice. These preclinical studies provided the rationale for colon cancer prevention trials in humans. A Phase IIb clinical study comparing the combination of DFMO and the NSAID sulindac versus placebo was conducted. Endpoints were colorectal tissue polyamine and prostaglandin E2 contents and overall toxicity to participants. Participants in the Phase IIb study served as a vanguard for a randomized, placebo-controlled prospective Phase III trial of the combination of DFMO and sulindac with the primary study endpoint the prevention of colon polyps. Seventy percent of participants will have completed the three years of treatment in December 2006.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalAmino Acids
Issue number2
StatePublished - Aug 2007
Externally publishedYes


  • Chemoprevention
  • Clinical trials
  • Colon cancer
  • Difluoromethylornithine
  • Nonsteroidal anti-inflammatory drugs
  • Polyamines

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Clinical Biochemistry


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