NEW YORK (Reuters Health) – Toremifene significantly decreases new vertebral fractures in younger men receiving androgen deprivation therapy (ADT) for prostate cancer, researchers report in an October 19th on-line paper in the Journal of Urology. And there was not a significantly elevated risk of venous thromboembolic events (VTEs).
Dr. Matthew R. Smith of Massachusetts General Hospital Cancer Center, Boston and colleagues note that ADT is associated with an increased fracture risk (See Reuters Health report 2011-07-22). Calcium and vitamin D supplements as well as bisphosphonates have been used as a preventative measure.
However, say the investigators, “To date there is minimal clinical evidence of agents that can significantly decrease the fracture risk in these patients and no agents have been approved by the United States Food and Drug Administration for fracture prevention in men receiving ADT for prostate cancer.”
Toremifene, which has been approved for use in metastatic breast cancer, is a second generation selective estrogen receptor modulator with beneficial estrogen-like agonist activity in bone and other favorable effects.
In a recent trial in men on ADT, it cut the incidence of new vertebral fractures by 50%, significantly increased bone mineral density (BMD) at the lumbar spine, hip and femoral neck, and significantly decreased bone turnover markers.
However, it also increased venous thromboembolic events (VTEs), but these were seen primarily in men with known risk factors, including being 80 years of age or more.
Given the improved risk-benefit profile in younger patients, the team conducted a post-hoc analysis in 847 participants less than 80 years old. They had been randomized to toremifene or placebo for up to 24 months.
The new vertebral fracture incidence was 1.0% in the active treatment group and 4.8% with placebo. The relative risk reduction was 79.5%. Toremifene significantly increased BMD at all measured sites. It also significantly decreased the incidence of nontraumatic fracture or greater than 7% bone loss within 24 months.
Toremifene was associated with a nonsignificant increase in the VTE rate compared with placebo (2.1% versus 1.0%). There were no fatal VTEs and no between group difference in the incidence of stroke.
The researchers conclude that “that men younger than 80 years are likely to receive the greatest benefit from toremifene therapy… without a concomitant increase in the risk of VTEs.”
Reference:
J Urol 2011.
