First Ever Prospective Fracture Study In Prostate Cancer Patients On ADT Reveals These Men Are At High Risk For Skeletal Fractures

Main Category: Prostate / Prostate Cancer
Also Included In: Bones / Orthopaedics
Article Date: 29 Apr 2009 - 1:00 PDT

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GTx, Inc. (Nasdaq: GTXI) announced that in a recent Phase III clinical trial of advanced prostate cancer patients being treated with androgen deprivation therapy (ADT), nearly one in four placebo group subjects developed bone fractures or critical bone loss (>7% loss) within two years. This analysis of placebo group data from the Phase III clinical trial evaluating toremifene 80 mg for the prevention of bone fractures in men with prostate cancer on ADT was presented yesterday in an oral presentation at the 2009 Annual Meeting of the American Urological Association in Chicago.

An analysis of placebo group subjects from the clinical trial demonstrates the risk of fracture for men with prostate cancer on ADT. During the two year trial, 9.9% of these men had a nontraumatic fracture (morphometric vertebral fracture or clinical fragility fracture), and nearly one in four, 23.9%, experienced either a nontraumatic fracture or greater than 7% bone loss, a predetermined level of bone loss at which men were considered to be at high risk for fracture and were removed from the study for safety reasons. These data are from the modified intent to treat population: subjects who had a minimum of one dose of study drug or placebo and at least one on study radiograph, n=970.

"The toremifene 80 mg Phase III clinical trial is the first large prospective study evaluating fractures in men with prostate cancer on ADT. The data from this clinical trial underscore that men on ADT are indeed at high risk for skeletal fractures," said Daniel 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. "ADT is an important treatment for men with prostate cancer. However, ADT itself over time can cause serious, life threatening side effects, such as fractures. As urologists who use ADT, it is our responsibility to monitor and to treat bone loss in our patients to reduce this high risk of fracture."

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 7.3 percent, placebo 11.8 percent), dizziness (treated 6.3 percent, placebo 5.0 percent), back pain (treated 5.9 percent, placebo 5.2 percent), and extremity pain (treated 5.0 percent, placebo 4.4 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 percent 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.

Source
GTx, Inc