Chemoprevention of prostate cancer with the polyamine synthesis inhibitor difluoromethylornithine.

Abstract

In vitro and in vivo preclinical results suggest that inhibition of polyamine synthesis inhibits the progression of prostate cancer. These findings has led to two clinical trials in patients at risk for invasive prostate cancer with difluoromethylornithine which specifically and irreversibly inhibits ornithine decarboxylase which catalyses the conversion of ornithine to putrescine the rate limiting step in polyamines synthesis. We have conducted a phase IIa one month and placebo randomized phase IIb 12 months trials in patients at increased risk for invasive prostate cancer. Favorable reduction in prostate polyamine levels and prostate volume was documented with no difference in clinical hearing changes. Patients with Gleason's VI lesions in a surveillance cohort would be appropriate candidates for a definitive risk reduction trial although the unavailability of validated biomarkers for invasive progression would require a large and lengthy study.

• Authors: Frank L Meyskens Jr, Anne R Simoneau, Eugene W Gerner
• Journal: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer (Recent Results Cancer Res) Vol. 202 Pg. 115-20 ( 2014) ISSN: 0080-0015 [Print] Germany
• PMID: 24531785 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)

Chemical References

• Enzyme Inhibitors
• Ornithine Decarboxylase Inhibitors
• Polyamines
• Ornithine Decarboxylase
• Eflornithine

Topics

• Biosynthetic Pathways (drug effects)
• Chemoprevention (methods)
• Eflornithine (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Humans
• Male
• Ornithine Decarboxylase (metabolism)
• Ornithine Decarboxylase Inhibitors
• Polyamines (metabolism)
• Prostatic Neoplasms (drug therapy, prevention & control)
• Treatment Outcome