Toremifene citrate versus placebo for treatment of bone loss and other complications of androgen deprivation therapy in patients with prostate cancer

Abstract

4597 Background: Patients with prostate cancer receiving androgen deprivation therapy (ADT) may experience side effects including bone loss (osteoporosis), hot flashes, and gynecomastia. Bone loss is of particular significance as a bone fracture in this population has been associated with a significant decrease in length of survival. Toremifene citrate (Acapodene™), a selective estrogen receptor modulator (SERM), has the potential to ameliorate many of these side effects of ADT and to improve quality of life. Methods: 46 consenting patients who had been on ADT for at least 12 months were randomized to 20 mg, 40 mg, or 60 mg of toremifene citrate or placebo administered orally once daily for 6 months. Assessments included bone mineral density (BMD) determination by dual energy X-ray absorptiometry (DEXA), bone turnover markers, and hot flashes. Results: Toremifene was well tolerated at all doses studied. Based on our own observations and recent reports in the literature, the antiandrogen bicalutamide can affect bone metabolism. To avoid confounding effects from bicalutamide, patients on bicalutamide were excluded from the analysis. Administration of 60 mg/day of toremifene (but not 20 mg/day or 40 mg/day) resulted in an increase of BMD after 6 months of therapy compared to a decrease in the placebo group (p < 0.01 ), as well as beneficial effects on other side effects of ADT. Conclusion: Toremifene administration resulted in a statistically significant increase in BMD after just 6 months of therapy in patients with prostate cancer, suggesting that toremifene, a SERM, is a promising agent to improve bone mineral density and quality of life in patients with prostate cancer receiving ADT. A long-term large scale trial is in progress to demonstrate the long term benefits of toremifene in prostate cancer patients receiving chronic ADT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx, Inc. GTx, Inc. GTx, Inc. GTx, Inc.