Public HealthGTx's Toremifene 80 Mg Increased Bone Mineral Density In Multiple Clinically Relevant Subpopulations Of Prostate Cancer Patients
GTx, Inc. (Nasdaq: GTXI) announced the presentation of data demonstrating that toremifene 80 mg treatment compared to placebo increased bone mineral density (BMD) in multiple clinically relevant subpopulations of men with prostate cancer on androgen deprivation therapy (ADT). The data, an analysis of results of the recent Phase III clinical trial evaluating toremifene 80 mg for the prevention of bone fractures and treatment of other estrogen deficiency side effects of androgen deprivation therapy in men with prostate cancer, were presented yesterday at the 2009 Annual Meeting of the American Society of Clinical Oncology.
Toremifene 80 mg treatment compared to placebo showed higher BMD at the spine and the hip in an analysis of specific subgroups defined by baseline characteristics such as time on ADT (above/below the median 2.3 years), age (above/below 70 years), baseline BMD (normal or low), prevalent fracture, country of origin (United States or Mexico), or use of calcium/vitamin D (Abstract # 5055: "The effect of toremifene citrate on BMD in men on ADT: A phase III clinical trial").
"Estrogen is the principal hormone responsible for maintaining bone integrity, and loss of estrogen due to androgen deprivation therapy can lead to increased risk of fracture in men with prostate cancer," said Daniel W. Lin, MD, Associate Professor and Chief of Urologic Oncology, Department of Urology, University of Washington School of Medicine, and a Principal Investigator in the study. "In the Phase III clinical trial, treatment with toremifene 80 mg, a selective estrogen receptor modulator, resulted in increased bone mineral density compared to placebo in men with prostate cancer on ADT and, most importantly, toremifene 80 mg treatment significantly reduced the risk of fracture."
Additional data from the clinical trial presented yesterday at ASCO demonstrated that in a univariate analysis, age greater than 70 years and degree of bone loss are independent predictors of fracture risk in men with prostate cancer on androgen deprivation therapy (Abstract # 9517: "Use of age and BMD to predict fracture risk in men on androgen deprivation therapy").
About the Study
The two year, double blind, placebo controlled, randomized study of 1,389 ADT patients was conducted at approximately 150 clinical sites in the United States and Mexico. The primary endpoint was new morphometric vertebral fractures measured by dual X-ray absorptiometry (DEXA). Key secondary endpoints included bone mineral density, lipid changes, hot flashes, and gynecomastia.
In the study, toremifene 80 mg treatment demonstrated statistically significant reductions compared to placebo in new morphometric vertebral fractures (the primary endpoint), in all nontraumatic fractures, and in first of either a nontraumatic fracture or greater than 7% bone loss. Toremifene 80 mg treatment compared to placebo also resulted in statistically significant increases in bone mineral density at the lumbar spine, hip, and femur; improvements in lipid profiles including a reduction in LDL, triglycerides and total cholesterol and an increase in HDL; and improvements in breast pain and tenderness.
Toremifene 80 mg was well tolerated. Among the most common adverse events that occurred in over 2 percent of study subjects were joint pain (treated 7.2 percent, placebo 11.5 percent), back pain (treated 5.9 percent, placebo 5.0 percent), dizziness (treated 5.9 percent, placebo 4.8 percent), and constipation (treated 4.2 percent, placebo 5.0 percent).
About ADT for Prostate Cancer
ADT, primary treatment for advanced prostate cancer, has improved survival in men with prostate cancer. Approximately 700,000 men with prostate cancer are being treated with ADT and an estimated 100,000 initiate ADT each year.
ADT is accomplished either surgically by removal of the testes, or more commonly by injection with LH releasing hormone (LHRH) agents. ADT works by reducing testosterone to castrate levels. The reduction in testosterone from ADT also results in very low estrogen levels, because estrogen is derived from testosterone in men. Estrogen deficiency side effects associated with ADT include high risk of skeletal fractures, adverse lipid changes, hot flashes, gynecomastia, depression, and memory loss.
Of patients on ADT, up to 77% develop significant bone loss, making them susceptible to fracture. Recent studies indicate that the annual risk of fracture in men on ADT is 5% to 8%. Fractures are serious and can reduce survival in men on ADT by more than three years.
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