Re : pharmacological prevention of side effects of androgen deprivation therapy, a new challenge?

Tombal, Bertrand [UCL]

Smith et al report the results of a double-blind, placebo-controlled phase 3 study designed to prospectively evaluate the benefit of the selective estrogen receptor modulator (SERM) toremifene in preventing long-term side effects of androgen deprivation therapy (ADT). The authors have assigned 1284 ADT-treated prostate cancer patients to toremifene (80 mg orally daily) or placebo for 2 yr. The study has reached the primary end point of reducing the rate of new vertebral fractures; the 2-yr incidence of new vertebral fracture was 4.9% in the placebo group versus 2.5% in the toremifene group, a significant relative risk reduction of 50% (p = 0.05). The incidence of any fracture was 10.1% with placebo and 6.3% with toremifene, a significant relative risk reduction of 38% (p = 0.036). Toremifene also reduced the rate of dyslipidemia: At 2 yr, high-density lipoprotein cholesterol increased by 7.2% and total cholesterol, low-density lipoprotein cholesterol, and triglycerides decreased by 4.7%, 7.0%, and 17.6%, respectively, in patients receiving toremifene (p < 0.001 for each comparison). Venous thromboembolic events (VTEs) were reported in 17 subjects (2.6%; 12 deep venous thromboses, 8 pulmonary embolisms) in the toremifene group and in 7 subjects (1.1%; 6 deep venous thromboses, 3 pulmonary embolisms) in the placebo group.