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Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.

Abstract：

BACKGROUND:A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course. OBJECTIVE: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. DESIGN, SETTING, AND PARTICIPANTS:Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot. INTERVENTION:GTx-758 and leuprolide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: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. RESULTS AND LIMITATIONS: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 1000 mg [p<0.001], GTx-758 2000 mg [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%). CONCLUSIONS: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. PATIENT SUMMARY: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. TRIAL REGISTRATION:Clinicaltrials.gov identifier NCT01615120.

journal_name

Eur Urol

journal_title

European urology

authors

Yu EY,Getzenberg RH,Coss CC,Gittelman MM,Keane T,Tutrone R,Belkoff L,Given R,Bass J,Chu F,Gambla M,Gaylis F,Bailen J,Hancock ML,Smith J,Dalton JT,Steiner MS

doi

10.1016/j.eururo.2014.06.011

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

334-41

issue

eissn

0302-2838

issn

1873-7560

pii

S0302-2838(14)00532-6

journal_volume

pub_type

杂志文章,多中心研究,随机对照试验

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Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer.