A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial.
androgen treatment in prostate cancer
body composition
muscle performance
quality of life
sexual function
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
13 07 2021
13 07 2021
Historique:
received:
18
02
2021
pubmed:
22
5
2021
medline:
21
10
2021
entrez:
21
5
2021
Statut:
ppublish
Résumé
Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer. In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers. Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73). Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.
Sections du résumé
BACKGROUND
Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer.
METHODS
In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers.
RESULTS
Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73).
CONCLUSIONS
Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.
Identifiants
pubmed: 34019661
pii: 6279839
doi: 10.1210/clinem/dgab361
pmc: PMC8277210
doi:
Substances chimiques
Androgens
0
Receptors, Androgen
0
Prostate-Specific Antigen
EC 3.4.21.77
Banques de données
ClinicalTrials.gov
['NCT02499497']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2171-2186Subventions
Organisme : NIA NIH HHS
ID : P30 AG031679
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Organisme : NIH HHS
ID : UL1TR002541
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR014502
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL132122
Pays : United States
Organisme : NINR NIH HHS
ID : R01NR014502
Pays : United States
Organisme : NIH HHS
ID : P30AG31679
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Références
J Pers Soc Psychol. 1988 Jun;54(6):1063-70
pubmed: 3397865
Nat Med. 2020 Feb;26(2):252-258
pubmed: 32042192
Health Qual Life Outcomes. 2015 May 17;13:60
pubmed: 25980742
CA Cancer J Clin. 2019 Sep;69(5):363-385
pubmed: 31184787
J Urol. 1997 Jul;158(1):155-9
pubmed: 9186344
J Urol. 2004 Sep;172(3):920-2
pubmed: 15310998
Eur Urol. 2014 Jan;65(1):115-23
pubmed: 24011426
J Clin Endocrinol Metab. 2010 Feb;95(2):639-50
pubmed: 20061435
Expert Opin Drug Saf. 2019 Nov;18(11):1065-1076
pubmed: 31495240
J Clin Endocrinol Metab. 2003 Jun;88(6):2673-81
pubmed: 12788872
J Urol. 2007 Feb;177(2):540-5
pubmed: 17222629
Eur J Prev Cardiol. 2019 Mar;26(5):533-543
pubmed: 30861690
JAMA. 2006 Nov 15;296(19):2351-61
pubmed: 17105798
Nat Clin Pract Endocrinol Metab. 2006 Mar;2(3):146-59
pubmed: 16932274
Gastroenterology. 1984 Aug;87(2):308-13
pubmed: 6428963
Mol Cell Endocrinol. 2008 Jun 25;288(1-2):30-7
pubmed: 18403105
J Androl. 2010 Sep-Oct;31(5):457-65
pubmed: 20133964
J Clin Endocrinol Metab. 2000 Dec;85(12):4500-10
pubmed: 11134099
Oncol Nurs Forum. 2008 Sep;35(5):786-93
pubmed: 18765324
Endocr Rev. 2004 Apr;25(2):276-308
pubmed: 15082523
J Urol. 2016 Oct;196(4):1082-9
pubmed: 27131465
J Urol. 2002 Jul;168(1):9-12
pubmed: 12050481
J Gerontol A Biol Sci Med Sci. 2013 Jan;68(1):87-95
pubmed: 22459616
Cancer. 1967 Nov;20(11):1871-8
pubmed: 4168724
J Sex Med. 2014 Apr;11(4):1063-1070
pubmed: 24443943
Clin Biochem. 2009 Jul;42(10-11):929-42
pubmed: 19362543
N Engl J Med. 2008 Mar 20;358(12):1250-61
pubmed: 18354103
J Clin Endocrinol Metab. 2006 Oct;91(10):3850-6
pubmed: 16882745
Clin Endocrinol (Oxf). 2005 Sep;63(3):280-93
pubmed: 16117815
J Sex Med. 2014 Oct;11(10):2562-70
pubmed: 24751323
JAMA. 1998 Sep 16;280(11):969-74
pubmed: 9749478
J Urol. 1981 Sep;126(3):372-5
pubmed: 7277602
Annu Rev Biochem. 1999;68:523-58
pubmed: 10872459
J Sex Med. 2009 Apr;6(4):1165-1170
pubmed: 19207277
Urology. 2010 Nov;76(5):1245-50
pubmed: 20350762
J Urol. 2016 Mar;195(3):699-705
pubmed: 26498057
JAMA. 2000 Jan 19;283(3):354-60
pubmed: 10647798
J Sex Marital Ther. 1997 Winter;23(4):291-304
pubmed: 9427208
Urology. 1999 Aug;54(2):346-51
pubmed: 10443736
Am J Health Syst Pharm. 2015 Apr 1;72(7):536-41
pubmed: 25788507
Biochem Biophys Res Commun. 2002 Sep 6;296(5):1051-7
pubmed: 12207878
Lancet Oncol. 2013 Apr;14(4):335-45
pubmed: 23499390
J Clin Endocrinol Metab. 2019 Dec 1;104(12):6238-6246
pubmed: 31504596
Urology. 2004 Oct;64(4):777-82
pubmed: 15491719
Pharm Res. 2012 Apr;29(4):1046-56
pubmed: 22167351
J Clin Endocrinol Metab. 2018 May 1;103(5):1715-1744
pubmed: 29562364
World J Urol. 2021 Sep;39(9):3223-3229
pubmed: 33034733
Mol Cell Endocrinol. 2018 Apr 15;465:134-142
pubmed: 28624515
N Engl J Med. 2013 Dec 19;369(25):2457
pubmed: 24350954
J Cachexia Sarcopenia Muscle. 2011 Sep;2(3):153-161
pubmed: 22031847
Urology. 2005 Jan;65(1):101-8
pubmed: 15667873
BJU Int. 2015 Mar;115(3):480-5
pubmed: 25046796
Urol Oncol. 2019 Oct;37(10):637-646
pubmed: 31296421
N Engl J Med. 2016 Feb 18;374(7):611-24
pubmed: 26886521
J Clin Endocrinol Metab. 2018 Mar 17;:
pubmed: 29562341
J Androl. 2003 Sep-Oct;24(5):688-98
pubmed: 12954659
J Natl Cancer Inst. 2008 Feb 6;100(3):170-83
pubmed: 18230794
J Lipid Res. 1991 Oct;32(10):1571-85
pubmed: 1797939
J Clin Endocrinol Metab. 1999 Aug;84(8):2647-53
pubmed: 10443654
J Am Geriatr Soc. 2008 Nov;56(11):2118-23
pubmed: 18811607
J Androl. 2009 Jan-Feb;30(1):1-9
pubmed: 18772485
Urology. 2008 Jul;72(1):172-6
pubmed: 18304619
J Sex Med. 2009 Mar;6 Suppl 3:234-8
pubmed: 19207279
Annu Rev Med. 2020 Jan 27;71:33-45
pubmed: 31613683
J Urol. 2017 Feb;197(2S):S171-S172
pubmed: 28010984
J Natl Cancer Inst. 2005 Aug 17;97(16):1204-10
pubmed: 16106025
J Urol. 2005 Feb;173(2):533-6
pubmed: 15643240