STOCKHOLM, SWEDEN (UroToday.com) - Androgen deprivation therapy (ADT) improves disease-free survival in men with advanced prostate cancer, but patients develop castration resistant prostate cancer (CRPC). One cause of CRPC is suboptimal castration, and 30-40% of men on LHRH agonists don’t achieve that level. There is growing literature showing that lower serum total testosterone levels correlate with improved outcomes. GTx-758 (Capesaris) is an oral, estrogen receptor-α agonist that increases sex hormone binding globulin (SHBG), lowers serum free testosterone levels, and ameliorates estrogen deficiency side effects associated with ADT. Dr. R. H. Getzenberg reported the preliminary results of the phase II trial at the 2014 EAU meeting in Stockholm, Sweden.
Enrolling patients in the U.S. and Europe, 38 men with mCRPC were enrolled and continued on their current form of ADT, along with a low dose of GTx-758, for at least 90 days. Exclusion criteria included men at increased risk for venous thrombolic events (VTE). All treated men had a ≥ 150% increase in SHBG levels. The drug was well tolerated, with gynecomastia (grade 2), nipple pain, loss of appetite, bone pain, and fatigue occurring in 10.5%, 7.9%, 7.9%, 7.9% and 7.9%, respectively. No thromboembolic events were reported. By RECIST criteria, 80% had stable disease at 90 days, while 6.7% demonstrated a partial response. By day 90, there was a median 57% reduction in PSA compared to baseline, and 100% of patients starting with a PSA < 0.3pg/mL achieved optimal castration. 60% of patients with a baseline PSA > 0.3pg/mL achieved optimal castration at 90 days.
In conclusion, the majority of patients on an LHRH agonist enrolled in this phase 2 study had suboptimal levels of serum free testosterone that were further lowered by GTx-758 administration. GTx-758 treatment resulted in stabilization and/or improvement in reported hot flashes and bone turnover. While this trial is ongoing, these preliminary findings show that GTx-758 has clinical effectiveness in men with mCRPC, as measured by decreasing free T and PSA, and is well tolerated.
Presented by R. H. Getzenberg at the 29th Annual European Association of Urology (EAU) Congress - April 11 - 15, 2014 - Stockholmsmässan - Stockholm, Sweden.
GTx Inc., Memphis USA
Written by Jeffrey J. Tomaszewski, MD, medical writer for UroToday.com