Journal article
Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer
European urology, v 67(2), pp 334-341
01 Feb 2015
PMID: 24968970
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course.
To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency–related side effects of androgen-deprivation therapy.
Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000mg/d, 2000mg/d, or leuprolide depot.
GTx-758 and leuprolide.
The primary end point was the proportion of patients achieving total testosterone ≤50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels.
Of 159 randomized patients, leuprolide reduced total testosterone to ≤50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000mg [p<0.001], GTx-758 2000mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%).
Although leuprolide reduced total testosterone to ≤50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs.
This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events.
Clinicaltrials.gov identifier NCT01615120.
Estrogen receptor α agonist GTx-758 was compared with leuprolide as initial androgen deprivation therapy in men with rising prostate-specific antigen (PSA) after local therapy. Although leuprolide lowered serum total testosterone more rapidly and to a greater extent than either of the two doses of GTx-758 evaluated, greater sex hormone-binding globulin increases and free testosterone decreases may explain the significantly greater PSA declines observed in men treated with GTx-758. GTx-758 also lowered the risk of hot flashes and decreased bone turnover.
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Details
- Title
- Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer
- Creators
- Evan Y. Yu - University of WashingtonRobert H. Getzenberg - GTx, Inc., Memphis, TN, USAChristopher C. Coss - GTx, Inc., Memphis, TN, USAMarc M. Gittelman - Aventura Hospital and Medical CenterThomas Keane - Medical University of South CarolinaRonald Tutrone - Chesapeake Urology AssociatesLaurence Belkoff - Urology AssociatesRobert Given - Urology of VirginiaJoel Bass - Associated Medical Professionals Urology, Syracuse, NY, USAFranklin Chu - San Bernardino Urological Associates, San Bernardino, CA, USAMichael Gambla - Regional UrologyFranklin Gaylis - Genesis HealthCareJames Bailen - Urology of IndianaMichael L. Hancock - GTx, Inc., Memphis, TN, USAJordan Smith - GTx, Inc., Memphis, TN, USAJames T. Dalton - GTx, Inc., Memphis, TN, USAMitchell S. Steiner - GTx, Inc., Memphis, TN, USA
- Publication Details
- European urology, v 67(2), pp 334-341
- Publisher
- Elsevier
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000347033500041
- Scopus ID
- 2-s2.0-84920720233
- Other Identifier
- 991021916913404721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Urology & Nephrology