联合雄激素阻断:比卡鲁胺的案例

Laurence Klotz , Paul Schellhammer
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引用次数: 34

摘要

联合治疗包括去势加抗雄激素。在药物或手术阉割后,雄激素受体可被肾上腺雄激素、低水平的残留睾酮和不依赖配体的激活剂激活。与单独去势相比,联合治疗的生存效益是泌尿外科研究最多的问题之一。比较联合治疗和单独去势的试验结果是可变的。对26项随机试验的荟萃分析表明,使用的抗雄激素类型是相关的。使用非甾体抗雄激素的联合治疗与统计学上显著的总体生存获益相关。相比之下,使用类固醇抗雄激素联合治疗与单独去势相比,生存率降低。比卡鲁胺50mg与尼鲁胺和氟他胺联合去势时相比有许多优点。这些包括改善的副作用,每日一次给药,通过与核辅激活因子和辅抑制因子的有利相互作用,更有效地抑制雄激素受体的雄激素非依赖性激活,以及在一项随机试验中提高生存率的证据。一项结合历史试验数据的分析表明,比卡鲁胺50mg加上雄激素剥夺可使前列腺癌死亡率的危险比(HR)降低20% (HR, 0.80;95% ci, 0.66-0.98)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combined Androgen Blockade: The Case for Bicalutamide

Combination therapy consists of castration plus an antiandrogen. Following medical or surgical castration, the androgen receptor can be activated by adrenal androgens, low levels of residual testosterone, and ligand-independent activators. The survival benefit of combination therapy compared with castration alone is one of the most studied questions in urology. Results from trials comparing combination therapy to castration alone are variable. A metaanalysis of 26 randomized trials indicated that the type of antiandrogen used is relevant. Combination therapy using nonsteroidal antiandrogens was associated with a statistically significant overall survival benefit. In contrast, combination therapy using steroidal antiandrogens was associated with reduced survival compared with castration alone. Bicalutamide 50 mg has a number of advantages compared with nilutamide and flutamide when used in combination with castration. These include an improved side-effect profile, once-daily dosing, more potent inhibition of androgen-independent activation of the androgen receptor through favorable interactions with nuclear coactivators and corepressors, and evidence for improved survival in one randomized trial. An analysis combining historic trial data suggests that bicalutamide 50 mg in addition to androgen deprivation may reduce the hazard ratio (HR) for prostate cancer mortality by 20% (HR, 0.80; 95% CI, 0.66-0.98).

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