Gartrell Benjamin A, Saad Fred
Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 E 210 St, Bronx, NY 10467, USA.
Centre Hospitalier de I'Université de Montréal, Montreal, Canada.
Ther Adv Urol. 2015 Aug;7(4):194-202. doi: 10.1177/1756287215592288.
The treatment armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has increased significantly over the past several years. Approved drugs associated with improved survival include androgen pathway-targeted agents (abiraterone acetate and enzalutamide), chemotherapeutics (docetaxel and cabazitaxel), an autologous vaccine (sipuleucel-T) and a radiopharmaceutical (radium-223). Abiraterone acetate, a prodrug of abiraterone, inhibits the CYP17A enzyme, a critical enzyme in androgen biosynthesis. Abiraterone has regulatory approval in mCRPC in both chemotherapy-naïve patients and in the post-docetaxel setting based on results from two randomized phase III studies. In the COU-AA-302 trial, abiraterone demonstrated significant improvement in the coprimary endpoints of radiographic progression-free survival and overall survival, as well as in a number of secondary endpoints including time until initiation of chemotherapy, time until opiate use for cancer-related pain, prostate-specific antigen progression-free survival and decline in performance status. Abiraterone is well-tolerated, although adverse events associated with this agent include abnormalities in liver function testing and mineralocorticoid-associated adverse events. This review evaluates the use of abiraterone in mCRPC prior to the use of chemotherapy.
在过去几年中,转移性去势抵抗性前列腺癌(mCRPC)的治疗手段显著增加。与生存期改善相关的获批药物包括雄激素通路靶向药物(醋酸阿比特龙和恩杂鲁胺)、化疗药物(多西他赛和卡巴他赛)、一种自体疫苗( sipuleucel-T)和一种放射性药物(镭-223)。醋酸阿比特龙是阿比特龙的前体药物,可抑制CYP17A酶,这是雄激素生物合成中的一种关键酶。基于两项随机III期研究的结果,阿比特龙在未经化疗的mCRPC患者以及多西他赛治疗后的患者中均获得了监管批准。在COU-AA-302试验中,阿比特龙在影像学无进展生存期和总生存期这两个共同主要终点以及包括开始化疗的时间、因癌症相关疼痛使用阿片类药物的时间、前列腺特异性抗原无进展生存期和体能状态下降等多个次要终点方面均显示出显著改善。阿比特龙耐受性良好,尽管与该药物相关的不良事件包括肝功能检查异常和盐皮质激素相关的不良事件。本综述评估了在化疗前使用阿比特龙治疗mCRPC的情况。