Castration-Resistant Prostate Cancer: From New Pathophysiology to New Treatment
Castration-Resistant Prostate Cancer: From New Pathophysiology to New Treatment
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DOI：
10.1016/j.eururo.2013.08.008
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发表时间：
2014-02-01
期刊：
影响因子：
23.4
通讯作者：
Saad, Fred
中科院分区：
文献类型：
--
作者：
Sridhar, Srikala S.;Freedland, Stephen J.;Saad, Fred
背景：直到最近，唯一获批的转移性去势抵抗性前列腺癌（mCRPC）药物是多西他赛化疗。但在过去的5年里，该领域的重大进展导致了5种新药的批准，每种新药都具有不同的作用机制，并在单独的随机3期试验中证明了总生存率的提高。许多这些新的药物，现在也正在评估在疾病的早期阶段，这可能最终导致更好的outcomes.Objective：总结目前的文献管理mCRPC，特别侧重于新的化疗方法，激素的方法，免疫治疗，放射性药物显示生存的好处，在3期临床试验。新兴的治疗在发展的后期阶段也进行了讨论briefly.Evidence收购：PubMed的全面搜索，确定了自2004年首次批准多西他赛以来，在mCRPC中评价的新疗法的研究。手动检索了主要国际会议的摘要，以识别mCRPC中处于后期开发阶段的新型药物研究。使用Clinical Trials.gov数据库查找mCRPC领域正在进行的临床试验。每一个新的代理商进行了详细的搜索，以确保这些代理商在其他阶段的疾病包括在relevant.Evidence synthesis：讨论的主要代理商是雄激素合成抑制剂醋酸阿比特龙，雄激素受体抑制剂恩杂鲁胺，新的紫杉烷化疗卡巴他赛，免疫治疗sipuleucel-T，和放射性药物镭223。其他新兴的药物和负面的3期结果的简要讨论也included.Conclusions：这是一个非常令人兴奋的时间在该领域的mCRPC，治疗进展改善了这种疾病的结果，虽然一旦转移的总体中位生存期仍然是一个令人沮丧的2-3年。现在的关键是了解如何最好地使用这些新药物，了解对它们的耐药性机制，继续开发新的治疗策略，并最终在疾病早期测试这些药物，以便治愈。(C)2013年欧洲泌尿外科协会。由Elsevier B出版。V.保留所有权利。
Context: Until recently, the only approved agent for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5 years, significant advances in the field have led to the approval of five new agents, each with different mechanisms of action and demonstrating improved overall survival in separate randomized phase 3 trials. Many of these novel agents are now also being evaluated in earlier stages of the disease, which may ultimately lead to even better outcomes.Objective: To summarize the current literature on the management of mCRPC with a particular focus on novel chemotherapy approaches, hormonal approaches, immunotherapy, and radiopharmaceuticals showing survival benefits in phase 3 clinical trials. Emerging therapies in late stages of development are also discussed briefly.Evidence acquisition: A comprehensive search of PubMed, identified studies pertaining to novel therapies evaluated in mCRPC since the initial approval of docetaxel in 2004. Abstracts from major international meetings were hand searched to identify studies of novel agents in late stage development in mCRPC. The Clinical Trials.gov database was used to find ongoing clinical trials in the area of mCRPC. A detailed search of each new agent was also performed to ensure that additional trials of these agents in other stages of the disease were included where relevant.Evidence synthesis: The main agents discussed are the androgen synthesis inhibitor abiraterone acetate, the androgen receptor inhibitor enzalutamide, the novel taxane chemotherapy cabazitaxel, the immunotherapy sipuleucel-T, and the radiopharmaceutical radium 223. Other emerging agents and a brief discussion of negative phase 3 results are also included.Conclusions: It is a very exciting time in the field of mCRPC, where therapeutic advances have improved outcomes in this disease, although once metastatic overall median survival remains a dismal 2-3 years. The key now will be to understand how best to use these new agents, understand the mechanisms of resistance to them, continue to develop novel treatment strategies, and ultimately test these agents earlier in the disease when cure may be possible. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.