Division of Hematology/Oncology, Department of Internal Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Curr Opin Oncol. 2013 May;25(3):252-60. doi: 10.1097/CCO.0b013e32835ff161.
Therapeutic options for men with metastatic prostate cancer are expanding. Here we discuss the scientific progress in this disease that led to approval of several agents in the last decade and highlight ongoing clinical investigation.
In androgen-sensitive disease, trials are evaluating the role of intermittent androgen-deprivation therapy, early chemotherapy, and novel targeted and hormonal therapies. For chemotherapy-naive, metastatic castration-resistant prostate cancer (mCRPC), abiraterone is effective. Trials with additional agents targeting androgen receptor (AR) signaling, such as TAK-700 and enzalutamide, are ongoing. Other agents in development target the endothelin pathway, angiogenesis, AR chaperones, and immune mechanisms. Docetaxel with prednisone remains the standard first-line chemotherapeutic regimen as trials incorporating novel agents with docetaxel have been negative. Postdocetaxel, enzalutamide improves survival. Early results with cabozantinib are encouraging, and phase III studies are ongoing. Denosumab and radium-223 reduce the risk of skeletal-related events (SREs), but only radium-223 improves survival.
Progress in understanding the disease biology and mechanisms of castration resistance led to significant therapeutic advancements, particularly in the setting of mCRPC in which several phase III trials, each incorporating agents with different mechanisms of action, have improved survival. As a result, new options exist, and the standard of care has changed significantly. Further advances are anticipated.
转移性前列腺癌患者的治疗选择正在不断扩大。本文讨论了导致过去十年批准几种药物的疾病科学进展，并重点介绍了正在进行的临床研究。
在雄激素敏感疾病中，试验正在评估间歇性雄激素剥夺治疗、早期化疗和新型靶向和激素治疗的作用。对于初次化疗的转移性去势抵抗性前列腺癌（mCRPC）患者，阿比特龙有效。正在进行针对雄激素受体（AR）信号的其他药物试验，如 TAK-700 和恩扎鲁胺。其他正在开发的药物靶向内皮素途径、血管生成、AR 伴侣和免疫机制。多西他赛联合泼尼松仍是标准的一线化疗方案，因为联合新型药物的试验结果为阴性。多西他赛后，恩扎鲁胺可提高生存率。卡博替尼的早期结果令人鼓舞，III 期研究正在进行中。地舒单抗和镭-223可降低骨骼相关事件（SRE）的风险，但只有镭-223可提高生存率。
对疾病生物学和去势抵抗机制的理解取得了进展，导致了显著的治疗进展，特别是在 mCRPC 中，几项 III 期试验，每个试验都包含具有不同作用机制的药物，都提高了生存率。因此，现在有了新的选择，治疗标准发生了重大变化。预计还会有进一步的进展。
