Department of Medicine, CHU Brugmann, Department of Medicine, Place Van Gehuchten, 1020 Brussels, Belgium.
Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal.
Nat Rev Urol. 2015 Jun;12(6):340-56. doi: 10.1038/nrurol.2015.90. Epub 2015 May 5.
Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development.
大多数转移性去势抵抗性前列腺癌（mCRPC）患者都会发生骨转移。它们会影响骨骼的结构完整性，表现为疼痛和骨骼相关事件（SREs），是导致患者残疾、生活质量（QOL）下降和死亡的主要原因。对骨转移的病理生理学的认识导致了能够改善临床结局的药物的发展，这表明管理全身性疾病和相关的骨骼事件很重要。在历史上，用放射性药物和外照射治疗 CRPC 骨转移主要是支持性治疗；然而，现在唑来膦酸和地舒单抗已成为 mCRPC 治疗策略的重要组成部分。这些药物可显著减少骨骼发病率并改善患者 QOL。镭-223 二氯化物是第一种在无内脏疾病的 mCRPC 患者中显示出生存改善、疼痛减轻和症状性骨骼事件减少的骨靶向药物。目前还有另外五种全身性药物被批准用于 mCRPC，这是基于它们提高生存率的能力。这些药物包括细胞毒性药物多西他赛和卡巴他赛、基于激素的治疗药物阿比特龙和恩扎鲁胺以及免疫治疗疫苗 sipuleucel-T。阿比特龙和恩扎鲁胺能够减少 SREs 并改善该环境下的生存率。针对肿瘤和骨细胞的新型药物正在临床开发中。
