The Perigee System is an effective treatment to repair anterior wall prolapse with a low rate of complications through a 2-year follow-up.

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104 Background: Androgen deprivation therapy (ADT) improves disease-free survival in men with advanced prostate cancer, but patients develop castrate resistant prostate cancer (CRPC); one of the causes of which is ineffective castration. Total serum testosterone (T) does not accurately predict prostatic levels of T. Further reduction of androgens in men with CRPC can result in improvement of survival. Herein we compare the effects GTx-758 an oral, selective estrogen receptor alpha (ERα) agonist versus leuprolide on total and free (unbound) serum T levels in men with advanced prostate cancer. Methods: In Phase II studies, men with advanced prostate cancer (n=164) received 1000 mg or 2000 mg GTx-758 daily or Lupron Depot (4 month), while men with CRPC (n=9) received 2000 mg GTx-758 daily. Serum concentrations of total T, free T, SHBG and PSA were determined at baseline and during treatment. Results: In ADT naïve advanced prostate cancer patients, 28 days of 1000 mg or 2000 mg daily GTx-758 or Lupron therapy castrated (T<50ng/dL) 50, 31 and 100% of patients, reducing mean serum total T in castrated patients to 23±14, 19±9 and 14±7 ng/dL, respectively. However, treatment with 1000 mg or 2000 mg GTx-758 daily reduced mean free T levels to a greater extent (0.9±0.7 and 0.7±0.7 pg/mL, respectively) than Lupron (1.7±1.1 pg/mL). Changes in PSA at 28 days were more closely associated with the observed changes in free T, with reductions of 74, 72 and 56% for 1000 mg, 2000 mg doses of GTx-758 and Lupron, respectively. In CRPC patients, 2000 mg GTx-758 daily did not further reduce serum total T levels, but did result in free T reductions and PSA decreases from baseline following 15 days of therapy in all of the men maintained on ADT with LHRH agonists alone. Conclusions: Although GTx-758 and LHRH based ADT both reduce total serum T and PSA levels in ADT naïve advanced prostate cancer patients, free T was rapidly reduced to a greater degree in the GTx-758 treated patients. In men with CRPC, GTx-758 therapy resulted in significant reductions in free T and resultant PSA declines. The ability of GTx-758 to reduce free T provides a unique mechanism to treat men with advanced prostate cancer and CRPC. Clinical trial information: NCT01326312.

222 Background: Men with advanced prostate cancer are being treated with androgen deprivation therapy (ADT) for longer periods of time. The use of ADT can be limited by estrogen deficiency side effects, including a loss of bone and a higher incidence of fractures. GTx-758 is an ERα agonist that lowers serum free testosterone greater than an LHRH agonist. Herein we compare the effects of GTx-758 and leuprolide on markers of bone turnover, C-terminal telopeptides and bone specific alkaline phosphatase, in men with advanced prostate cancer treated with ADT. Methods: In a Phase II study (G200705), men with advanced prostate cancer (n=159) received 1000 mg or 2000 mg of GTx-758 daily or leuprolide. Serum samples were collected and analyzed by a reference laboratory. C-terminal telopeptides (pg/ml) and bone specific alkaline phosphatase (U/L) were measured as indicators of bone turnover. All p values describe the comparison of the GTx-758 treatment groups to the leuprolide treated men at day 120. Results: Men receiving the 1000 mg and 2000 mg doses of GTx-758 had lower C-terminal telopeptide levels with a mean percentage change of -56.9 ± 12.5 and -54.8 ± 23.1, respectively, as compared with an increase of 46.0 ± 48.9 percentage in the men receiving the leuprolide (p<0.001). Similarly, bone specific alkaline phosphatase levels were lower in men treated with GTx-758, with mean percentage changes of-28.5 ± 11.7 and -19.8 ± 14.7, respectively, compared with an increase of 8.1 ± 24.3 percent in the leuprolide treated group (p<0.001). As a result of an increased risk of venous thromboembolic events (VTEs) at these higher doses of GTx-758, the trial was stopped prior to its completion and not all of the men on the study reached the 120 day treatment dates (71 evaluable). Conclusions: Patients receiving GTx-758 experienced a significant decrease in markers of bone turnover indicating potential improvement and not a loss of bone on ADT. Since changes in bone mineral density are a major side effect that can negatively affect the quality of life in men on ADT, the improvements in bone turnover observed in men treated with GTx-758 could be significant. A Phase II clinical trial utilizing lower doses of GTx-758 (G200712) is currently being performed. Clinical trial information: NCT01326312.