The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial

Anne R. Simoneau, Eugene W. Gerner, Raymond B Nagle, Argyrios Ziogas, Sharon Fujikawa-Brooks, Hagit Yerushalmi, Thomas E. Ahlering, Ronald Lieberman, Christine E. McLaren, Hoda Anton-Culver, Frank L. Meyskens

Research output: Contribution to journalArticle

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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 cm3) than those on placebo (2.95 cm3; 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)292-299
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2008

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Eflornithine
Chemoprevention
Polyamines
Prostate
Placebos
Putrescine
Prostatic Neoplasms
Ornithine Decarboxylase
Prostate-Specific Antigen
Hearing
Hyperplasia
Histology
Randomized Controlled Trials
Biomarkers
Genotype
Biopsy
Health

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

The effect of difluoromethylornithine on decreasing prostate size and polyamines in men : Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial. / Simoneau, Anne R.; Gerner, Eugene W.; Nagle, Raymond B; Ziogas, Argyrios; Fujikawa-Brooks, Sharon; Yerushalmi, Hagit; Ahlering, Thomas E.; Lieberman, Ronald; McLaren, Christine E.; Anton-Culver, Hoda; Meyskens, Frank L.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 17, No. 2, 01.02.2008, p. 292-299.

Research output: Contribution to journalArticle

Simoneau, AR, Gerner, EW, Nagle, RB, Ziogas, A, Fujikawa-Brooks, S, Yerushalmi, H, Ahlering, TE, Lieberman, R, McLaren, CE, Anton-Culver, H & Meyskens, FL 2008, 'The effect of difluoromethylornithine on decreasing prostate size and polyamines in men: Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial', Cancer Epidemiology Biomarkers and Prevention, vol. 17, no. 2, pp. 292-299. https://doi.org/10.1158/1055-9965.EPI-07-0658
Simoneau, Anne R. ; Gerner, Eugene W. ; Nagle, Raymond B ; Ziogas, Argyrios ; Fujikawa-Brooks, Sharon ; Yerushalmi, Hagit ; Ahlering, Thomas E. ; Lieberman, Ronald ; McLaren, Christine E. ; Anton-Culver, Hoda ; Meyskens, Frank L. / The effect of difluoromethylornithine on decreasing prostate size and polyamines in men : Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial. In: Cancer Epidemiology Biomarkers and Prevention. 2008 ; Vol. 17, No. 2. pp. 292-299.
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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 cm3) than those on placebo (2.95 cm3; 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. Conclusion: 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.",
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T2 - Results of a year-long phase IIb randomized placebo-controlled chemoprevention trial

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AU - Gerner, Eugene W.

AU - Nagle, Raymond B

AU - Ziogas, Argyrios

AU - Fujikawa-Brooks, Sharon

AU - Yerushalmi, Hagit

AU - Ahlering, Thomas E.

AU - Lieberman, Ronald

AU - McLaren, Christine E.

AU - Anton-Culver, Hoda

AU - Meyskens, Frank L.

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N2 - 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 cm3) than those on placebo (2.95 cm3; 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. Conclusion: 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.

AB - 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 cm3) than those on placebo (2.95 cm3; 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. Conclusion: 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.

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