Toremifene Reduces Vertebral Fractures in Men on Androgen Deprivation Therapy for Prostate Cancer: Presented at AACR

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Title: Toremifene Reduces Vertebral Fractures in Men on Androgen Deprivation Therapy for Prostate Cancer: Presented at AACR
URL: http://www.pslgroup.com/dg/21FB32.htm
Doctor's Guide
April 21, 2008

By Sophie Bainbridge

SAN DIEGO -- April 18, 2008 -- The oral selective oestrogen receptor modulator toremifene significantly reduced the rate of vertebral fractures in men with advanced prostate cancer receiving androgen deprivation therapy (ADT), according to results from a phase 3, randomised, placebo-controlled trial.

Matthew R. Smith, MD, PhD, Director of Genitourinary Medical Oncology, Massachusetts General Hospital Cancer Center, and Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts, presented the findings here at the American Association for Cancer Research (AACR) Annual Meeting.

Androgen deprivation therapy with a gonadotropin-releasing hormone agonist is the cornerstone of treatment for advanced and recurrent prostate cancer. Although this therapy improves outcomes in certain settings, it has a variety of adverse effects related to oestrogen deficiency, including osteoporosis, fractures, hot flashes, gynaecomastia or breast symptoms, and changes in blood lipid levels.

Patients were enrolled from 150 centres in the United States and Mexico. Dr. Smith presented data on 696 patients randomised to toremifene and 686 to placebo for 24 months. All study participants had low bone mineral density and were aged 70 years or older and thus were considered at high risk for fractures.

Toremifene significantly increased bone mineral density of the hip and spine compared with placebo (P < .001 for each comparison), Dr. Smith said.

Men who were randomised to treatment with toremifene 80 mg/day had significantly fewer new morphometric vertebral fractures than did subjects in the placebo group and reduced their fracture risk in half (2.5% vs 4.9%; relative risk 0.50; P < .05), Dr. Smith reported in a late-breaking oral presentation on April 15.

In addition to toremifene's effect on fractures, the trial also demonstrated improvements to the other ADT-linked adverse effects. With regard to blood lipid levels, toremifene decreased total cholesterol (P = .001), low-density lipoprotein cholesterol (P = .018), and triglycerides (P < .0001) and increased levels of high-density lipoprotein cholesterol compared with placebo.

There were also statistically significant improvements in gynaecomastia (P = .003). And in patients experiencing 6 or more hot flashes per day at baseline, toremifene reduced the number of hot flashes per day by an average 4.7 compared with a reduction of 1.6 with placebo (P = .03).

Toremifene had a good safety profile and was well tolerated versus placebo. Among the most common adverse events were joint pain (7% vs 12%, respectively), dizziness (6% vs 5%, respectively), back pain (6% vs 5%, respectively), and extremity pain (5% vs 4%, respectively).

Venous thromboembolic events (VTEs), which included deep vein thrombosis and pulmonary embolism, occurred in 2% of toremifene patients and 1% of the placebo group. Dr. Smith explained that the majority of VTEs occurred in men at high risk for such events, including older patients (>80 years), those who had a recent surgical procedure, those with prior VTEs, and men who were immobile. When these high-risk patients were excluded from the analysis, the rates of VTEs were similar to placebo.

"As a medical oncologist treating prostate cancer patients, I have seen first hand how the serious side effects of androgen deprivation therapy not only have an impact on a man's quality of life but can also be life threatening," Dr. Smith said in a press briefing. "The results of this trial are exciting, as they demonstrate that toremifene citrate 80 mg prevents fractures and also treats other side effects of ADT."

Toremifene is being developed by GTx, Inc.

[Presentation title: A Phase III Randomized Controlled Trial of Toremifene to Prevent Fractures and Other Adverse Effects of Androgen Therapy in Men With Prostate Cancer. Abstract LB-241]

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