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.
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.
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%).
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 .
Keywords: Bone turnover, Estrogen receptor, Free testosterone, GTx-758, Leuprolide, Prostate cancer, Sex hormone-binding globulin.
a University of Washington, Seattle, WA, USA
b GTx, Inc., Memphis, TN, USA
c South Florida Medical Research, Aventura, FL, USA
d Medical University of South Carolina, Charleston, SC, USA
e Chesapeake Urology, Towson, MD, USA
f Urologic Consultants of Southeastern Pennsylvania, Bala Cynwyd, PA, USA
g Urology of Virginia, Virginia Beach, VA, USA
h Associated Medical Professionals Urology, Syracuse, NY, USA
i San Bernardino Urological Associates, San Bernardino, CA, USA
j Central Urology Group, Columbus, OH, USA
k Genesis Healthcare Partners, San Diego, CA, USA
l First Urology, Jeffersonville, IN, USA
Corresponding author. University of Washington, Seattle Cancer Care Alliance, Department of Medicine, Division of Oncology, 825 Eastlake Avenue E, Box 358081, G4-800, Seattle, WA 98109, USA. Tel. +1 206 288 7595; Fax: +1 206 288 2042.
© 2014 European Association of Urology, Published by Elsevier B.V.