Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate …
YY Evan, RH Getzenberg, CC Coss, MM Gittelman… - European urology, 2015 - Elsevier
YY Evan, RH Getzenberg, CC Coss, MM Gittelman, T Keane, R Tutrone, L Belkoff, R Given…
European urology, 2015•ElsevierBackground 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 …
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 …
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.
Elsevier