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• W2094642217 abstract "No AccessJournal of UrologyAdult Urology: Oncology: Prostate/Testis/Penis/Urethra1 Sep 2004EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCERis corrected byRE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCERRE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCER G.L. ANDRIOLE, P. HUMPHREY, P. RAY, M.E. GLEAVE, J. TRACHTENBERG, L.N. THOMAS, C.B. LAZIER, and R.S. RITTMASTER G.L. ANDRIOLEG.L. ANDRIOLE Financial interest and/or other relationship with Abbott Laboratories, Antigenics, Bambridge Scientific, Barr Laboratories, Bion Diagnostic, CD Searle, Cell Pathways, GlaxoSmithKline, Merck & Co., Pharmacia and Zeneca. More articles by this author , P. HUMPHREYP. HUMPHREY Nothing to disclose. More articles by this author , P. RAYP. RAY Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author , M.E. GLEAVEM.E. GLEAVE Financial interest and/or other relationship with OncoGenex, TAP, Astra Zeneca, Aventis and Isis Pharmaceuticals. More articles by this author , J. TRACHTENBERGJ. TRACHTENBERG Nothing to disclose. More articles by this author , L.N. THOMASL.N. THOMAS Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author , C.B. LAZIERC.B. LAZIER Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author , and R.S. RITTMASTERR.S. RITTMASTER Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000136430.37245.b9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5α-reductase (5αR) types 1 and 2 (5αR1 and 5αR2). Suppression of DHT formation by 5αR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5αR2 is the dominant enzyme in the prostate, evidence indicates that 5αR1 may be up-regulated in some prostate cancers. This suggests that dual inhibition of both isoenzymes may be more effective than suppression of 5αR2 alone in prostate cancer treatment or prevention. In this short-term pilot study we examined the effect of the dual 5αR inhibitor dutasteride on markers of tumor regression. Materials and Methods: A total of 46 men with clinically staged T1 or T2 prostate cancer were randomized to receive 5 mg per day of placebo or dutasteride for 6 to 10 weeks before radical prostatectomy. Resected tissues were analyzed to determine the effect of dutasteride on intraprostatic androgen levels, and indices of apoptosis and microvessel density (MVD) in malignant tissue, as well as degree of atrophy in benign tissue. Results: Treatment with dutasteride caused a 97% decrease in intraprostatic DHT and was associated with a trend toward increased apoptosis. In patients receiving dutasteride for 45 days or more, a significant increase in apoptosis and a trend toward decreased MVD in prostate cancer tissue was observed. Dutasteride treatment was also associated with an 18% decrease in mean benign epithelial cell width compared with placebo (p < 0.0001). Conclusions: In this pilot study dutasteride treatment resulted in almost complete suppression of intraprostatic DHT, increased apoptosis and a trend toward decreased MVD. These findings suggest that short-term treatment with dutasteride can cause regression in some prostate cancers. References 1 : The dihydrotestosterone (DHT) hypothesis of prostate cancer and its therapeutic implications. Prostate1986; 9: 343. Google Scholar 2 : Kinetic parameters of 5 alpha-reductase activity in stroma and epithelium of normal, hyperplastic, and carcinomatous human prostates. J Clin Endocrinol Metab1988; 67: 806. Google Scholar 3 : Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab1992; 75: 1022. Google Scholar 4 : The influence of finasteride on the development of prostate cancer. N Engl J Med2003; 349: 215. 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Link, Google Scholar 17 : Selectivity of finasteride as an in vivo inhibitor of 5 alpha-reductase isozyme enzymatic activity in the human prostate. J Urol1999; 161: 332. Link, Google Scholar 18 : Quantitation of apoptotic activity following castration in human prostatic tissue in vivo. Prostate2003; 54: 212. Google Scholar 19 : Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation. Cancer1999; 85: 1822. Google Scholar 20 : Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial. BJU Int2002; 90: 561. Google Scholar From the Divisions of Urology (GLA), and Pathology and Immunology (PH), Washington University, St. Louis, Missouri, Division of Urology, Cook County Hospital, Chicago, Illinois (PR), Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina (RSR), United States, and Division of Urology, University of British Columbia, Vancouver, British Columbia (MEG), Division of Urology, University of Toronto, Toronto, Ontario (JT), and Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (LNT, CBL), Canada© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byLee M, Moussa A, Yu C, Kattan M, Magi-Galluzzi C and Jones J (2018) Multifocal High Grade Prostatic Intraepithelial Neoplasia is a Risk Factor for Subsequent Prostate CancerJournal of Urology, VOL. 184, NO. 5, (1958-1962), Online publication date: 1-Nov-2010.Thomas L, Douglas R, Lazier C, Gupta R, Norman R, Murphy P, Rittmaster R and Too C (2018) Levels of 5α-Reductase Type 1 and Type 2 are Increased in Localized High Grade Compared to Low Grade Prostate CancerJournal of Urology, VOL. 179, NO. 1, (147-151), Online publication date: 1-Jan-2008.Tindall D and Rittmaster R (2018) The Rationale for Inhibiting 5α-Reductase Isoenzymes in the Prevention and Treatment of Prostate CancerJournal of Urology, VOL. 179, NO. 4, (1235-1242), Online publication date: 1-Apr-2008.Serfling R, Shulman M, Thompson G, Xiao Z, Benaim E, Roehrborn C and Rittmaster R (2018) Quantifying the Impact of Prostate Volumes, Number of Biopsy Cores and 5α-Reductase Inhibitor Therapy on the Probability of Prostate Cancer Detection Using Mathematical ModelingJournal of Urology, VOL. 177, NO. 6, (2352-2356), Online publication date: 1-Jun-2007.Marks L, Roehrborn C and Andriole G (2018) Prevention of Benign Prostatic Hyperplasia DiseaseJournal of Urology, VOL. 176, NO. 4, (1299-1306), Online publication date: 1-Oct-2006. (2018) RE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCERJournal of Urology, VOL. 173, NO. 4, (1434-1435), Online publication date: 1-Apr-2005.Andriole G, Humphrey P, Ray P, Gleave M, Trachtenberg J, Thomas L, Lazier C and Rittmaster R (2018) RE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCERJournal of Urology, VOL. 173, NO. 4, (1433-1434), Online publication date: 1-Apr-2005.Related articlesJournal of Urology9 Nov 2018RE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCERJournal of Urology9 Nov 2018RE: EFFECT OF THE DUAL 5α-REDUCTASE INHIBITOR DUTASTERIDE ON MARKERS OF TUMOR REGRESSION IN PROSTATE CANCER Volume 172Issue 3September 2004Page: 915-919 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordstestosterone 5-alpha-reductaseprostatic neoplasmsapoptosisMetricsAuthor Information G.L. ANDRIOLE Financial interest and/or other relationship with Abbott Laboratories, Antigenics, Bambridge Scientific, Barr Laboratories, Bion Diagnostic, CD Searle, Cell Pathways, GlaxoSmithKline, Merck & Co., Pharmacia and Zeneca. More articles by this author P. HUMPHREY Nothing to disclose. More articles by this author P. RAY Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author M.E. GLEAVE Financial interest and/or other relationship with OncoGenex, TAP, Astra Zeneca, Aventis and Isis Pharmaceuticals. More articles by this author J. TRACHTENBERG Nothing to disclose. More articles by this author L.N. THOMAS Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author C.B. LAZIER Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author R.S. RITTMASTER Financial interest and/or other relationship with GlaxoSmithK-line. More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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