[So, do NOT think about using for PCT!!!]
Yu EY, Getzenberg RH, Coss CC, et al. Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer. Eur Urol. http://www.europeanurology.com/article/S0302-2838(14)00532-6/abstract/selective-estrogen-receptor-alpha-agonist-gtx-758-decreases-testosterone-with-reduced-side-effects-of-androgen-deprivation-therapy-in-men-with-advanced-prostate-cancer
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 alpha 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 1000mg/d, 2000mg/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 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%).
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.
Yu EY, Getzenberg RH, Coss CC, et al. Selective Estrogen Receptor Alpha Agonist GTx-758 Decreases Testosterone with Reduced Side Effects of Androgen Deprivation Therapy in Men with Advanced Prostate Cancer. Eur Urol. http://www.europeanurology.com/article/S0302-2838(14)00532-6/abstract/selective-estrogen-receptor-alpha-agonist-gtx-758-decreases-testosterone-with-reduced-side-effects-of-androgen-deprivation-therapy-in-men-with-advanced-prostate-cancer
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 alpha 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 1000mg/d, 2000mg/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 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%).
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.
