Princess Margaret Hospital, Toronto, ON, Canada.
Durham VA Medical Center and Duke University Medical Center, Durham, NC, USA.
Eur Urol. 2014 Feb;65(2):289-99. doi: 10.1016/j.eururo.2013.08.008. Epub 2013 Aug 11.
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.
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.
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.
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.
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.
直到最近，转移性去势抵抗性前列腺癌（mCRPC）唯一获批的治疗药物是多西他赛化疗。但在过去的 5 年中，该领域的重大进展导致了 5 种新药物的批准，每种药物的作用机制不同，并在单独的随机 3 期临床试验中显示出改善的总生存期。许多这些新型药物目前也正在疾病的早期阶段进行评估，这可能最终会带来更好的结果。
总结目前关于 mCRPC 管理的文献，特别关注新型化疗方法、激素方法、免疫疗法和放射性药物在 3 期临床试验中显示出生存获益的情况。还简要讨论了处于晚期开发阶段的新兴疗法。
对 PubMed 进行了全面检索，确定了自 2004 年多西他赛首次批准以来评估 mCRPC 新型疗法的研究。对主要国际会议的摘要进行了手工检索，以确定 mCRPC 晚期开发中新型药物的研究。使用 ClinicalTrials.gov 数据库查找 mCRPC 领域的正在进行的临床试验。还对每个新药物进行了详细搜索，以确保在相关情况下纳入这些药物在疾病其他阶段的其他试验。
讨论的主要药物是雄激素合成抑制剂阿比特龙醋酸酯、雄激素受体抑制剂恩扎鲁胺、新型紫杉烷化疗药物卡巴他赛、免疫疗法 sipuleucel-T 和放射性药物镭 223。还包括其他新兴药物和阴性 3 期结果的简要讨论。
mCRPC 领域目前是一个非常令人兴奋的时期，治疗进展改善了这种疾病的预后，尽管一旦转移，总体中位生存期仍然很差，只有 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，当治愈可能成为可能时。
