George Daniel J, Kantoff Philip W, Lin Daniel W
Duke Medical Center, Durham, North Carolina, USA.
Clin Adv Hematol Oncol. 2011 Jun;9(6):1-11; discussion 11-5.
Historically, the treatment of metastatic castration-resistant prostate cancer (CRPC) has been limited to chemotherapeutic regimens that did not improve patient survival. In 2004, clinical studies began to demonstrate significant improvements in patient outcomes, including overall survival, with docetaxel versus mitoxantrone chemotherapy. Since these pivotal trials, the combination of docetaxel plus prednisone has become a standard of care for patients with metastatic CRPC. However, the limited survival benefit achieved with this regimen prompted several investigations into the development of alternative therapeutic options. Recent advances have now led to an unprecedented number of new drug approvals within the past year, providing many new treatment options for patients with metastatic CRPC. Sipuleucel-T, considered a new paradigm in cancer treatment, is the first such immunotherapeutic agent approved by the US Food and Drug Administration. Other successes include abiraterone acetate, the first androgen biosynthesis inhibitor, and cabazitaxel, a novel microtubule inhibitor, both of which have demonstrated improved survival following docetaxel failure. The bone-targeting agent denosumab, also recently approved in this setting, offers these patients significant improvement in the prevention of skeletal-related events. The data supporting the approval of each of these agents are described in this monograph, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies. The experts also discuss several of the issues regarding the introduction of these novel agents into clinical practice for metastatic CRPC patients.
从历史上看，转移性去势抵抗性前列腺癌（CRPC）的治疗一直局限于那些无法提高患者生存率的化疗方案。2004年，临床研究开始表明，与米托蒽醌化疗相比，多西他赛化疗在包括总生存期在内的患者预后方面有显著改善。自这些关键试验以来，多西他赛加泼尼松的联合用药已成为转移性CRPC患者的标准治疗方案。然而，该方案所带来的有限生存获益促使人们对替代治疗方案的开发进行了多项研究。最近的进展使得在过去一年里有前所未有的大量新药获批，为转移性CRPC患者提供了许多新的治疗选择。西妥昔单抗被认为是癌症治疗的一种新范式，是美国食品药品监督管理局批准的首个此类免疫治疗药物。其他成功药物包括首个雄激素生物合成抑制剂醋酸阿比特龙和新型微管抑制剂卡巴他赛，这两种药物在多西他赛治疗失败后均显示出了生存改善。最近在这种情况下也获批的骨靶向药物地诺单抗，在预防骨相关事件方面为这些患者带来了显著改善。本专著描述了支持这些药物获批的相关数据，以及转移性CRPC的当前治疗方法和新型治疗及策略的正在进行的临床试验。专家们还讨论了将这些新型药物引入转移性CRPC患者临床实践的若干问题。
