a 2nd Department of Surgery, Aretaieion Academic Hospital, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece.
b 1st Department of Urology, Laikon General Hospital, School of Medicine , National and Kapodistrian University of Athens , Athens , Greece.
Expert Opin Investig Drugs. 2018 Jun;27(6):553-559. doi: 10.1080/13543784.2018.1484107. Epub 2018 Jun 18.
Prostate cancer (PCa) is the most common cancer in elderly males. Androgen deprivation therapy (ADT) is still the cornerstone of initial treatment; however, the vast majority of patients develop castration-resistant prostate cancer (CRPC). Several studies with numerous androgen receptor (AR)-directed agents have emerged since the approval of abiraterone acetate and enzalutamide. One of these agents is apalutamide, which seems to be a promising AR antagonist for the treatment of CRPC. Areas covered: The authors review Phase I, II, and III studies for apalutamide, in a large spectrum of PCa (from low-risk to metastatic CRPC [mCRPC]) patients as sole treatment or in the setting of combined therapy. Expert opinion: Apalutamide is an oral, investigational, AR antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. It has shown favorable safety profile and therapeutic index in Phase I studies, good tolerance and efficacy in patients with high-risk CRPC in Phase II studies. Also, results were promising in a recent phase III study in patients with non-mCRPC who were at high risk for the development of metastasis. These data may offer potential advantages over the second-generation antiandrogens.
前列腺癌（PCa）是老年男性中最常见的癌症。去势治疗（ADT）仍然是初始治疗的基石；然而，绝大多数患者会发展为去势抵抗性前列腺癌（CRPC）。自从醋酸阿比特龙和恩扎卢胺获得批准以来，已经出现了许多针对雄激素受体（AR）的药物的研究。其中一种药物是阿帕鲁胺，它似乎是一种有前途的用于治疗 CRPC 的 AR 拮抗剂。
作者综述了阿帕鲁胺的 I 期、II 期和 III 期研究，这些研究涵盖了广泛的前列腺癌（从低危到转移性 CRPC [mCRPC]）患者，作为单一治疗或联合治疗的方案。
阿帕鲁胺是一种口服的、研究性的 AR 拮抗剂，靶向 AR 配体结合域，防止 AR 核转位、DNA 结合和 AR 基因靶点的转录。在 I 期研究中，它表现出良好的安全性和治疗指数，在 II 期研究中，在高危 CRPC 患者中具有良好的耐受性和疗效。此外，在最近一项针对高危转移风险的非 mCRPC 患者的 III 期研究中，结果也很有前景。这些数据可能比第二代抗雄激素具有潜在优势。
