Toremifene reduced fractures in androgen deprivation-treated prostate cancer

SAN DIEGO — Toremifene at 80 mg significantly decreased new morphometric vertebral fractures in men receiving androgen deprivation therapy for prostate cancer, according to new data presented yesterday at the 2008 Annual Meeting of the American Association for Cancer Research.

“To our knowledge, this is the first large randomized controlled trial to evaluate fractures in men in any setting,” Matthew Smith, MD, PhD, director of research, genitourinary unit of oncology at Massachusetts General Hospital, said during his presentation on April 15.

The use of androgen deprivation therapy, which has almost doubled in the last decade, is associated with several adverse events, most importantly increased fracture and decreased bone mineral density.

Smith and colleagues at Massachusetts General examined 1,382 men aged >70 years with histologically documented prostate cancer and ≥6 months of androgen deprivation therapy. The study was conducted at 150 sites in the United States and Mexico. Patients were randomly assigned to either 80 mg of toremifene (Fareston, GTX Inc.) daily or placebo for two years.

In a modified intent-to-treat analysis of patients (n=970) with more than one on-study radiograph, there was a 50% reduction in morphometric vertebral fractures (P=.03). The total intent-to-treat population (n=1,382) had a 55% reduction in fractures (P=.023). Toremifene significantly reduced incidence of any nontraumatic fracture by 33%. The drug also increased bone mineral density at the lumbar spine, hip and femoral neck, compared with placebo (P<.001).

Researchers observed secondary endpoints of improved lipid profiles, decreased breast pain and decreased hot flashes in the toremifene group.

Overall, the rates of adverse events were similar between the two groups. Increased risk of venous thromboembolic events was observed in the treatment group, but the risk appeared to be restricted to the first year of treatment and patients who had major risk factors for venous thromboembolic events at baseline. – by Leah Lawrence

Vertebral fracture is something that clearly is of great importance. There are a wide variety of drugs that can be used to treat it, but the long and short of it is that there is a huge variety and not every variety is one size fits all. If you have ever treated a patient on androgen deprivation therapy there are a significant number of metabolic changes. Toremifene has improved most of these metabolic changes, so there is clearly a benefit. Is toremifene replacing or adding to current osteoporotic regimens for men on androgen deprivation therapy? This is a pivotal study using another class of antiosteoporosis drugs, but it is prospective, so overall impact is still to be determined.

– Susan F. Slovin, MD

Assistant Member, Genitourinary Oncology Service
Memorial Sloan-Kettering Cancer Center

For more information:

Smith MR. # LB-241. Presented at: 2008 Annual Meeting of the American Association for Cancer Research; April 12-16, 2008; San Diego.