title: The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: results of a year-long phase IIb randomized placebo-controlled chemoprevention trial.
abstract: BACKGROUND
  Prostate cancer is a major health issue, and prevention of prostate cancer and/or its progression will yield benefits for men. Difluoromethylornithine (DFMO) is an antiproliferative agent, inhibiting ornithine decarboxylase, the first enzyme in the polyamine pathway, and has been studied as a therapeutic and chemopreventive agent. The prostate has high levels of tissue polyamines and has shown sensitivity to DFMO both in vitro and in vivo.
  
  
  METHODS
  Eighty-one men participated in a 1-year randomized trial of placebo or DFMO. Prostate volume determination and biopsy of the prostate for histology and polyamine content were done at baseline and after 12 months. Other biomarker variables were assessed, including total and free prostate-specific antigen and prostate-specific antigen doubling time.
  
  
  RESULTS
  Compared with baseline, men receiving DFMO had a smaller increase in prostate volume (0.14 cm(3)) than those on placebo (2.95 cm(3); P = 0.0301) at 1 year. In addition, DFMO caused a 60.8% reduction of prostate putrescine levels compared with a 139.5% increase in the placebo arm (P = 0.0014). Stratification by ornithine decarboxylase genotype showed that DFMO reduced prostate volume (P = 0.029) and putrescine levels (P = 0.0053) in the AA + GA group but not in the GG group. There were no grade 3 or 4 toxicities. There was no clinical ototoxicity, with one subclinical grade 2 hearing decline on audiogram.
  
  
  CONCLUSIONS
  In this randomized placebo-controlled trial, DFMO induced a decrease of prostate putrescine levels and rate of prostate growth. The potential of this compound for prostate cancer or hyperplasia should be further studied.
authors.affiliation: Department of Medicine, University of California, Irvine, 101 The City Drive, Route 81, Building 55, Room 304, Orange, CA 92868, USA. asimonea@uci.edu
authors.forename: Anne R
authors.initials: AR
authors.lastname: Simoneau
authors.forename: Eugene W
authors.initials: EW
authors.lastname: Gerner
authors.forename: Ray
authors.initials: R
authors.lastname: Nagle
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ziogas
authors.forename: Sharon
authors.initials: S
authors.lastname: Fujikawa-Brooks
authors.forename: Hagit
authors.initials: H
authors.lastname: Yerushalmi
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Ahlering
authors.forename: Ronald
authors.initials: R
authors.lastname: Lieberman
authors.forename: Christine E
authors.initials: CE
authors.lastname: McLaren
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood; D001706:Biopsy; D000518:Eflornithine / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011073:Polyamines; D017430:Prostate-Specific Antigen; D000518:Eflornithine