Enzalutamide versus abiraterone acetate for the treatment of men with metastatic castration-resistant prostate cancer

被引:23
|
作者
Zhang, Tian [1 ]
Zhu, Jason [2 ]
George, Daniel J. [3 ,4 ]
Armstrong, Andrew J. [3 ,4 ]
机构
[1] Duke Univ, Med Ctr, Div Med Oncol, Duke Canc Inst,Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[3] Duke Canc Inst, Dept Med, Div Med Oncol, Durham, NC 27710 USA
[4] Duke Canc Inst, Dept Surg, Div Urol, Durham, NC 27710 USA
关键词
abiraterone acetate; androgen receptor-V7; castration-resistant prostate cancer; cross-resistance; enzalutamide; resistance; I CLINICAL-TRIAL; ANDROGEN RECEPTOR; ANTITUMOR-ACTIVITY; CONFERS RESISTANCE; INCREASED SURVIVAL; DOCETAXEL; VARIANTS; MDV3100; KETOCONAZOLE; CYP17;
D O I
10.1517/14656566.2015.995090
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain. Areas covered: We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17. In addition to discussing the clinical evidence, we also address evolving evidence of mechanisms of resistance and clinical cross-resistance during sequential therapy with these agents. Expert opinion: AA and enzalutamide have both demonstrated tolerability and clinical benefit for multiple outcomes in patients with CRPC, in both post-chemotherapy and pre-chemotherapy settings. Both agents target the androgen-signaling pathway and have similar efficacy; however, they differ in prednisone use and their toxicity profiles, impacting the decision of upfront therapy. Mechanisms of resistance emerging after treatment include both alterations in AR signaling as well as mechanisms that bypass the AR. Retrospective analyses have demonstrated evidence that sequential treatment with these agents results in limited clinical benefit, supporting mechanisms of cross-resistance. Trials are ongoing to determine optimal timing, sequence and combination of these agents.
引用
收藏
页码:473 / 485
页数:13
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