Cancer Research Lab

The selective estrogen receptor modulator toremifene significantly increases bone mineral density and improves lipid profiles in men receiving androgen deprivation therapy for advanced prostate cancer.

That’s according to two planned interim analyses of an ongoing multicenter study presented today in Orlando at The Prostate Cancer Symposium, co-sponsored by the American Society of Clinical Oncology, the American Society of Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

The study includes 1,392 men 50 years of age or older receiving androgen deprivation therapy for advanced prostate cancer who were randomly assigned to toremifene (80 mg/day) or placebo for 24 months.

BMD, measured in 200 men, showed that after 12 months toremifene was associated with a significant increase in BMD at the lumbar spine (+1.6%), hip (+0.7%), and femur (+0.2%). In contrast and as expected, the changes in men in the placebo arm were -0.7%, -1.3%, and -1.3%, respectively at these sites.

“The magnitude of the bone mineral density improvement with toremifene is quite comparable, if not superior, to that observed in studies of raloxifene in postmenopausal women,” Dr. Matthew Smith of Massachusetts General Hospital Cancer Center, Boston reported at a press briefing.

“There is great concern now that not only does androgen-deprivation therapy increase the risk for fractures but that it also has a variety of other metabolic adverse effects,” Dr. Smith also noted. “We have recently shown that androgen-deprivation therapy is associated with greater risk of coronary heart disease and incident myocardial infarction. Adverse treatment-related changes in lipid profiles may be at least part of this mechanism,” he explained.

In the second planned interim analysis, lipid levels, analyzed after one year in 197 men, showed “striking and highly clinically significant” improvements in men taking toremifene.

Compared with placebo, toremifene was associated with a 7.1% decrease in total cholesterol, a 9.0% decrease in LDL cholesterol, and a 20.1% decrease in triglycerides, as well as a 5.4% increase in HDL cholesterol.

It’s possible, Dr. Smith said, that the lipid changes observed with toremifene “would predict improvement in cardiovascular outcomes” in men on androgen-deprivation therapy.

In summary, Dr. Smith said in a statement, the results suggest that toremifene has “the potential not only to reduce the risk of fractures in men with advanced prostate cancer, but also to improve lipid levels, addressing another significant side effect of the standard treatment for this disease.”