Dinh Jesse Aidan, Baker Danial, Chahal Manpreet
Washington State University College of Pharmacy, Spokane, Washington, USA.
Consult Pharm. 2016;31(10):581-592. doi: 10.4140/TCP.n.2016.581.
To provide an overview of the efficacy, tolerability, drug interactions, dosing, and administration issues associated with enzalutamide, abiraterone, and radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).
MEDLINE and Web of Science were used to search for relevant articles using a key-word search (enzalutamide, abiraterone, radium-223, and phase 3). No restriction was placed on the date of publication.
STUDY SELECTION/DATA EXTRACTION: Located articles were reviewed and selected based on their relevance to the treatment of mCRPC. Articles were selected if they focused on double-blind, randomized controlled, phase 3 studies conducted in humans and published in English. Other resources were used for the information pertaining to the drug's mechanism of action, administration, drug interactions, and adverse effects. Data extraction for the clinical application (e.g., efficacy, adverse reactions, and monitoring) was obtained from the identified clinical trials and the drug's approved labeling by one of the authors and validated by a second author.
Abiraterone, enzalutamide, and radium-223 have been shown to improve radiographic progression-free survival and overall survival before or after treatment with docetaxel. Abiraterone and enzalutamide has been able to delay time to the initiation of docetaxel. Major adverse effects vary with these medications. Enzalutamide-based therapy was associated with increased risk of seizures. Abiraterone-based therapy was associated with increased mineralocorticoid excess. Radium-223-based therapy was associated with increased risk of myelosuppression.
In clinical trials, abiraterone, enzalutamide, and radium-223 improved the radiographic progression-free survival and overall survival in patients with mCRPC compared with placebo. Each drug has unique adverse effects requiring monitoring of routine laboratory tests and for severe associated symptoms. To better define the role of these drugs in the treatment of mCRPC, clinical trials designed to directly compare these drugs' survival rate is necessary.
概述恩杂鲁胺、阿比特龙和镭 - 223用于治疗转移性去势抵抗性前列腺癌（mCRPC）患者时的疗效、耐受性、药物相互作用、给药剂量及给药相关问题。
使用MEDLINE和科学网通过关键词搜索（恩杂鲁胺、阿比特龙、镭 - 223和3期）查找相关文章。对发表日期无限制。
研究选择/数据提取：根据文章与mCRPC治疗的相关性对检索到的文章进行审查和选择。若文章聚焦于在人类中进行的、以英文发表的双盲、随机对照3期研究，则予以入选。其他资源用于获取有关药物作用机制、给药、药物相互作用及不良反应的信息。临床应用的数据提取（如疗效、不良反应和监测）由一位作者从已识别的临床试验及药物批准标签中获取，并由另一位作者进行验证。
已证明阿比特龙、恩杂鲁胺和镭 - 223可改善多西他赛治疗之前或之后的影像学无进展生存期和总生存期。阿比特龙和恩杂鲁胺能够延迟多西他赛开始使用的时间。这些药物的主要不良反应各不相同。基于恩杂鲁胺的治疗与癫痫发作风险增加相关。基于阿比特龙的治疗与盐皮质激素过多风险增加相关。基于镭 - 223的治疗与骨髓抑制风险增加相关。
在临床试验中，与安慰剂相比，阿比特龙、恩杂鲁胺和镭 - 223改善了mCRPC患者的影像学无进展生存期和总生存期。每种药物都有独特的不良反应，需要监测常规实验室检查及严重相关症状。为更好地明确这些药物在mCRPC治疗中的作用，有必要设计直接比较这些药物生存率的临床试验。
