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 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.
Written by:
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. Are you the author?
University of Washington, Seattle, WA, USA; GTx, Inc., Memphis, TN, USA; South Florida Medical Research, Aventura, FL, USA; Medical University of South Carolina, Charleston, SC, USA; Chesapeake Urology, Towson, MD, USA; Urologic Consultants of Southeastern Pennsylvania, Bala Cynwyd, PA, USA; Urology of Virginia, Virginia Beach, VA, USA; Associated Medical Professionals Urology, Syracuse, NY, USA; San Bernardino Urological Associates, San Bernardino, CA, USA; Central Urology Group, Columbus, OH, USA; Genesis Healthcare Partners, San Diego, CA, USA; First Urology, Jeffersonville, IN, USA.
Reference: Eur Urol. 2014 Jun 24. pii: S0302-2838(14)00532-6.
doi: 10.1016/j.eururo.2014.06.011
PubMed Abstract
PMID: 24968970
UroToday.com Prostate Cancer Section
