Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
Eur Urol. 2011 Aug;60(2):279-90. doi: 10.1016/j.eururo.2011.04.038. Epub 2011 May 4.
Prostate cancer (PCa) is the most common noncutaneous malignancy and the second leading cause of cancer mortality amongst men in the Western world. Up to 40% of men diagnosed with PCa will eventually develop metastatic disease, and although most respond to initial medical or surgical castration, progression to castration resistance is universal. The average survival for patients with castration-resistant prostate cancer (CRPC) is 2-3 yr.
To discuss the biologic rationale and evidence supporting current management of patients with CRPC and to review promising novel agents.
Electronic databases (PubMed, ClinicalTrials.gov), relevant journals, and conference proceedings were searched manually for preclinical studies, clinical trials, and biomarker analyses focused on the treatment of CRPC. Keywords included castrate resistant prostate cancer and: targeted therapy, novel therapy, immunotherapy, androgen therapy, bone therapy, mechanisms, biomarkers, and trial endpoints; no time range was specified. Information pertaining to current studies was discussed with key opinion leaders.
We focus on the efficacy and safety of approved agents, promising therapies that have proceeded to phase 3 evaluation, and those that have enhanced our understanding of the biology of CRPC. Biomarkers are considered in the context of novel targeted agents and immunotherapy.
CRPC has many targets. Four new agents with different mechanisms of action have recently been shown to have positive results in large phase 3 randomized trials, and have already been approved in the United States for CRPC: cabazitaxel, sipuleucel-T, denosumab, and abiraterone acetate. With our improved understanding of tumor biology and the incorporation of new prognostic and molecular biomarkers into clinical trials, we are making progress in the management of patients with CRPC.
前列腺癌（PCa）是西方世界中最常见的非皮肤恶性肿瘤，也是男性癌症死亡的第二大主要原因。多达 40%的被诊断患有 PCa 的男性最终会发展为转移性疾病，尽管大多数人对初始的医学或手术去势治疗有反应，但进展为去势抵抗是普遍的。患有去势抵抗性前列腺癌（CRPC）的患者的平均存活时间为 2-3 年。
讨论支持目前治疗 CRPC 患者的生物学原理和证据，并综述有前途的新型药物。
手动搜索电子数据库（PubMed、ClinicalTrials.gov）、相关期刊和会议记录，以获取专注于 CRPC 治疗的临床前研究、临床试验和生物标志物分析的研究。关键词包括去势抵抗性前列腺癌和：靶向治疗、新型治疗、免疫治疗、雄激素治疗、骨治疗、机制、生物标志物和试验终点；未指定时间范围。与主要意见领袖讨论了与当前研究相关的信息。
我们专注于已批准药物的疗效和安全性、已进入 3 期评估的有前途的治疗方法，以及那些增强了我们对 CRPC 生物学理解的方法。生物标志物在新型靶向药物和免疫疗法的背景下进行了讨论。
CRPC 有许多靶点。最近四项具有不同作用机制的新型药物在大型 3 期随机试验中显示出积极结果，并且已经在美国获得 CRPC 的批准：卡巴他赛、sipuleucel-T、地舒单抗和阿比特龙乙酸盐。随着我们对肿瘤生物学的理解的提高，以及将新的预后和分子生物标志物纳入临床试验，我们在 CRPC 患者的管理方面取得了进展。
