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 a 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. Â© 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Yu, Evan Y.; Getzenburg, Robert H.; Coss, Christopher C.; Gittelman, Mark M.; Keane, Thomas; Tutrone, Ronald; Belkoff, Laurence; Given, Robert; Bass, Joel; and al., et, "Selective estrogen receptor alpha agonist GTx-758 decreases testosterone with reduced side effects of androgen deprivation therapy in men with advanced prostate cancer" (2015). PCOM Scholarly Papers. 1399.
This article was published in European Urology, Volume 67, Issue 2.The published version is available at http://dx.doi.org/10.1016/j.eururo.2014.06.011.
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