Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
J Urol. 2011 Dec;186(6):2239-44. doi: 10.1016/j.juro.2011.07.090. Epub 2011 Oct 19.
Androgen deprivation therapy is associated with an increased fracture risk. In a recent phase III trial toremifene significantly decreased vertebral fractures in men on androgen deprivation therapy. Similar to other selective estrogen receptor modulators, toremifene was associated with an increase in venous thromboembolic events with the greatest risk in men 80 years old or older. In this post hoc analysis we evaluated the efficacy and safety of toremifene in men younger than 80 years.
This analysis included 847 men younger than 80 years, of whom 430 received toremifene 80 mg by mouth daily and 417 received placebo for up to 24 months. The primary end point was new vertebral fractures. Secondary end points included fragility fractures, bone mineral density and safety.
Compared with placebo, toremifene decreased the relative risk of new vertebral fractures by 79.5% (95% CI 29.8-94.0, p <0.005). The new vertebral fracture incidence was 1.0% for toremifene and 4.8% for placebo (absolute risk reduction 3.8%). Compared with placebo, toremifene significantly decreased the incidence of nontraumatic fracture or greater than 7% bone loss by 24 months (p <0.0001). Toremifene also significantly increased bone mineral density at all measured sites (all comparisons p <0.001). The incidence of venous thromboembolic events was similar in the toremifene and placebo groups (2.1% and 1.0%, respectively, p = 0.26). The rates of other adverse events were also similar between the groups.
Toremifene significantly decreased new vertebral fractures in men younger than 80 years receiving androgen deprivation therapy for prostate cancer. The risk of venous thromboembolic events was lower than in the overall study population, suggesting an improved risk-benefit profile in younger men.
雄激素剥夺疗法与骨折风险增加有关。在最近的一项托瑞米芬 III 期临床试验中，托瑞米芬显著降低了接受雄激素剥夺疗法的男性的椎体骨折发生率。与其他选择性雌激素受体调节剂类似，托瑞米芬与静脉血栓栓塞事件的增加相关，风险最大的是 80 岁或以上的男性。在本事后分析中，我们评估了托瑞米芬在 80 岁以下男性中的疗效和安全性。
本分析包括 847 名 80 岁以下的男性，其中 430 名接受托瑞米芬 80mg 口服，每日一次，417 名接受安慰剂，最长达 24 个月。主要终点是新发椎体骨折。次要终点包括脆性骨折、骨密度和安全性。
与安慰剂相比，托瑞米芬降低了新发椎体骨折的相对风险 79.5%（95%CI 29.8-94.0，p<0.005）。托瑞米芬组的新发椎体骨折发生率为 1.0%，安慰剂组为 4.8%（绝对风险降低 3.8%）。与安慰剂相比，托瑞米芬在 24 个月时显著降低了非外伤性骨折或骨丢失超过 7%的发生率（p<0.0001）。托瑞米芬还显著增加了所有测量部位的骨密度（所有比较 p<0.001）。托瑞米芬组和安慰剂组静脉血栓栓塞事件的发生率相似（分别为 2.1%和 1.0%，p=0.26）。两组其他不良事件的发生率也相似。
托瑞米芬显著降低了接受前列腺癌雄激素剥夺治疗的 80 岁以下男性的新发椎体骨折发生率。静脉血栓栓塞事件的风险低于总体研究人群，提示在年轻男性中具有改善的风险效益比。
