University of Washington, Seattle, WA, USA.
GTx, Inc., Memphis, TN, USA.
Eur Urol. 2015 Feb;67(2):334-41. doi: 10.1016/j.eururo.2014.06.011. Epub 2014 Jun 24.
A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course.
To assess the ability of an oral selective estrogen receptor α agonist (GTx-758) to lower testosterone concentrations compared with leuprolide while minimizing estrogen deficiency-related side effects of androgen-deprivation therapy.
DESIGN, SETTING, AND PARTICIPANTS: Hormone-naive advanced prostate cancer patients were randomized to oral GTx-758 1000 mg/d, 2000 mg/d, or leuprolide depot.
GTx-758 and leuprolide.
The primary end point was the proportion of patients achieving total testosterone ≤ 50 ng/dl by day 60. Secondary end points included serum free testosterone, prostate-specific antigen (PSA), sex hormone-binding globulin, hot flashes, bone turnover markers, and insulin-like growth factor (IGF)-1 levels.
Of 159 randomized patients, leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients than GTx-758 by day 60 (43.4%, 63.6%, and 88.2% of subjects receiving GTx-758 1000 mg [p<0.001], GTx-758 2000 mg [p=0.004], and leuprolide, respectively). GTx-758 reduced free testosterone and PSA earlier and to a greater degree than leuprolide. GTx-758 led to fewer hot flashes, decreases in bone turnover markers, and alterations in IGF-1 compared with leuprolide. A higher incidence of venous thromboembolic events (VTEs) was seen with GTx-758 (4.1%) compared with leuprolide (0.0%).
Although leuprolide reduced total testosterone to ≤ 50 ng/dl in a greater proportion of patients compared with GTx-758, GTx-758 was superior in lowering free testosterone and PSA. GTx-758 reduced estrogen deficiency side effects of hot flashes, bone loss, and insulin resistance but with a higher incidence of VTEs.
This paper reports findings that leuprolide lowered total testosterone more than GTx-758 but that GTx-758 lowered free testosterone and prostate-specific antigen more than leuprolide. GTx-758 also reduced estrogen deficiency side effects, albeit at a higher rate of vascular events.
Clinicaltrials.gov identifier NCT01615120.
对于晚期前列腺癌患者，尤其是在疾病早期，仍然需要新的治疗方法。
评估口服选择性雌激素受体 α 激动剂（GTx-758）与亮丙瑞林相比降低睾酮浓度的能力，同时最大限度地减少去势治疗相关的雌激素缺乏副作用。
设计、地点和参与者：激素初治的晚期前列腺癌患者被随机分配至口服 GTx-758 1000mg/d、2000mg/d 或亮丙瑞林。
GTx-758 和亮丙瑞林。
主要终点是第 60 天达到总睾酮≤50ng/dl 的患者比例。次要终点包括游离睾酮、前列腺特异性抗原（PSA）、性激素结合球蛋白、热潮红、骨转换标志物和胰岛素样生长因子（IGF）-1 水平。
在 159 名随机患者中，亮丙瑞林在第 60 天降低总睾酮至≤50ng/dl 的患者比例大于 GTx-758（分别接受 GTx-758 1000mg、GTx-758 2000mg 和亮丙瑞林的患者中，43.4%、63.6%和 88.2%，p<0.001）。GTx-758 比亮丙瑞林更早、更显著地降低游离睾酮和 PSA。与亮丙瑞林相比，GTx-758 导致更少的热潮红、骨转换标志物降低和 IGF-1 改变。与亮丙瑞林相比，GTx-758 出现更高的静脉血栓栓塞事件（VTE）发生率（4.1%对 0.0%）。
尽管亮丙瑞林在降低总睾酮至≤50ng/dl 的患者比例上优于 GTx-758，但 GTx-758 在降低游离睾酮和 PSA 方面更优。GTx-758 降低了热潮红、骨丢失和胰岛素抵抗等雌激素缺乏的副作用，但 VTE 发生率更高。
本文报道了亮丙瑞林降低总睾酮的效果优于 GTx-758，但 GTx-758 降低游离睾酮和 PSA 的效果优于亮丙瑞林。GTx-758 还降低了雌激素缺乏的副作用，但血管事件发生率更高。
Clinicaltrials.gov 标识符 NCT01615120。
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