Hadfield Matthew J, Lyall Vikram, Holle Lisa M, Dennison Morgan
Department of Medical Oncology, The Warren Alpert Medical School, Brown University, Providence, RI, USA.
Section of Urology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
Ann Pharmacother. 2023 Nov;57(11):1302-1311. doi: 10.1177/10600280231155441. Epub 2023 Feb 24.
To review pharmacology, efficacy, safety, and considerations for use, of second-generation androgen receptor (AR) antagonists in treatment of nonmetastatic castrate-resistant prostate cancer (M0CRPC).
Conducted search in PubMed and Google scholar (January, 1, 2002-December 31, 2022), using relevant terms.
Relevant English-language studies, conducted in humans evaluating second-generation AR antagonists for M0CRPC, and additional articles and package inserts were considered.
Apalutamide, darolutamide, and enzalutamide are effective in delaying the time to development of metastatic prostate cancer in men with M0CRPC with a rapid prostate-specific antigen (PSA) doubling time (<10 months). No head-to-head, randomized, clinical trials have been conducted. The most common adverse effects include fatigue and hypertension, and quality of life is maintained in most patients. Cost is similar among the agents (~$15,000/month). Drug-drug interactions vary among these agents and should be considered, when selecting therapy as well as likely adherence. Darolutamide is administered twice daily with the others once daily.
Second-generation AR antagonists are effective in reducing time to development of metastatic disease and prolonging overall survival in patients with M0CRPC and a PSA doubling time of <10 months. Recent imaging advances may alter how we evaluate outcomes.
Second-generation AR antagonists improve disease control and overall survival. Generally, they are well tolerated and QOL is maintained. Selection of the best agent is based on the adverse effect profile, potential for drug- and disease-interactions, administration, cost, and patient preference.
综述第二代雄激素受体（AR）拮抗剂在治疗非转移性去势抵抗性前列腺癌（M0CRPC）中的药理学、疗效、安全性及使用注意事项。
于2002年1月1日至2022年12月31日期间，在PubMed和谷歌学术上使用相关术语进行检索。
纳入评估第二代AR拮抗剂用于M0CRPC的相关英文人体研究，以及其他文章和药品说明书。
阿帕他胺、达罗他胺和恩杂鲁胺可有效延缓M0CRPC且前列腺特异性抗原（PSA）倍增时间较快（<10个月）的男性发生转移性前列腺癌的时间。尚未进行直接对比的随机临床试验。最常见的不良反应包括疲劳和高血压，大多数患者的生活质量得以维持。这些药物的成本相似（约15,000美元/月）。这些药物之间的药物相互作用各不相同，在选择治疗方案以及考虑患者可能的依从性时应予以考虑。达罗他胺每日给药两次，其他药物每日给药一次。
第二代AR拮抗剂可有效减少M0CRPC且PSA倍增时间<10个月的患者发生转移性疾病的时间并延长总生存期。近期的影像学进展可能会改变我们评估疗效的方式。
第二代AR拮抗剂可改善疾病控制和总生存期。总体而言，它们耐受性良好，生活质量得以维持。最佳药物的选择基于不良反应谱、药物和疾病相互作用的可能性、给药方式、成本以及患者偏好。
