Androgen deprivation therapy (ADT) is established as the mainstay treatment for advanced prostate cancer. ADT deprives prostate cancer of testosterone, its most important growth factor, and causes the cancer to go into remission for years. ADT is so effective that prostate cancer has become a chronic disease: patients now typically die with, rather than from, prostate cancer. More than 100,000 men in the U.S. begin androgen deprivation therapy each year, and it is estimated that nearly one million men are currently being treated with ADT.

ADT	SERM
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In men, estrogen is derived from testosterone. By lowering testosterone, ADT virtually depletes estrogen levels. Consequently, patients on ADT experience a multitude of hormone-induced side effects such as osteoporosis, adverse lipid changes, hot flashes, gynecomastia, impaired cognition and increased risk for cardiovascular disease.

GTx recently completed a pivotal Phase III clinical trial evaluating toremifene 80 mg for the treatment of multiple side effects of ADT for advanced prostate cancer. 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. Other key secondary endpoints included bone mineral density, lipid changes, hot flashes, and gynecomastia.

Other endpoints
Patients treated with toremifene 80 mg compared to placebo had statistically significant increases in bone mineral density in the lumbar spine, hip, and femur skeletal sites (each p<0.0001). Toremifene 80 mg treatment also resulted in a decrease in total cholesterol (p=0.011), LDL (p=0.018), and triglycerides (p<0.0001), and an increase in HDL (p=0.001). There were also statistically significant improvements in gynecomastia (p=0.003). In patients experiencing 6 or more hot flashes per day at baseline who were not being treated with megestrol acetate (Megace®), toremifene 80 mg was shown to reduce the number of hot flashes by an average 4.7 hot flashes per day compared to placebo patients who had a reduction of 1.6 hot flashes per day (p=0.03).

Safety
Toremifene 80 mg had a favorable safety profile and was well tolerated. Among the most common adverse events that occurred in over 2% of study subjects were joint pain (treated 7.3%, placebo 11.8%), dizziness (treated 6.3%, placebo 5.0%), back pain (treated 5.9%, placebo 5.2%), and extremity pain (treated 5.0%, placebo 4.4%).

Based on these findings, GTx plans to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) by late summer 2008.