Amino Acids

, Volume 33, Issue 2, pp 189–195

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

  • E. W. Gerner
  • F. L. MeyskensJr
  • S. Goldschmid
  • P. Lance
  • D. Pelot
Review Article

DOI: 10.1007/s00726-007-0515-2

Cite this article as:
Gerner, E., Meyskens, F., Goldschmid, S. et al. Amino Acids (2007) 33: 189. doi:10.1007/s00726-007-0515-2


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.

Keywords: Colon cancer – Chemoprevention – Polyamines – Difluoromethylornithine – Nonsteroidal anti-inflammatory drugs – Clinical trials



Adenomatous polyposis coli


cyclooxygenase 1


cyclooxygenase 2




familial adenomatous polyposis


hereditary non-polyposis colon cancer


non-steroidal anti-inflammatory drugs


ornithine decarboxylase


peroxisomal proliferator activated receptor γ


spermidine/spermine N1-acetyltransferase


single nucleotide polymorphism

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • E. W. Gerner
    • 1
  • F. L. MeyskensJr
    • 2
  • S. Goldschmid
    • 3
  • P. Lance
    • 3
  • D. Pelot
    • 2
  1. 1.Arizona Cancer Center, Department of Cell Biology and AnatomyThe University of ArizonaTucsonUSA
  2. 2.Chao Family Comprehensive Cancer Center, Department of MedicineThe University of CaliforniaIrvineUSA
  3. 3.Arizona Cancer Center, Department of MedicineThe University of ArizonaTucsonUSA