Veterans Administration Medical Center, Boston, MA, USA.
Ann Pharmacother. 2012 Nov;46(11):1518-28. doi: 10.1345/aph.1R169. Epub 2012 Nov 7.
To review the activity of 3 new agents approved for the management of advanced castration-resistant prostate cancer (CRPC): sipuleucel-T, cabazitaxel, and abiraterone acetate.
Literature was accessed through MEDLINE (1977-June 2012) and abstracts from the American Society of Clinical Oncology (2000-2012) using the terms castration-resistant and hormone-refractory prostate cancer, sipuleucel-T, cabazitaxel, abiraterone, Provenge, Jevtana, and Zytiga. Reference citations from publications identified were also reviewed.
Articles identified from the data sources in English on human subjects were evaluated.
Options for patients with CRPC have been limited, with little to offer those who failed or could not tolerate docetaxel-based therapy. Three new drugs, with very different mechanisms of action, have changed that and will undoubtedly change the treatment paradigm for these patients. Each agent has demonstrated an impact on patient survival. Sipuleucel-T, the first immunotherapy approved for treatment of CRPC, improved median overall survival by 4.1 months and reduced the risk of death by 22% in a placebo-controlled trial of asymptomatic patients. Sipuleucel-T can be administered prior to docetaxel-based therapy. Cabazitaxel, a taxane chemotherapy agent, improved median overall survival by 2.4 months and reduced the risk of death by 30% in a Phase 3 trial of patients whose cancer progressed during or after docetaxel-based therapy. Abiraterone acetate, a hormonal therapy, improved median overall survival by 3.9 months and reduced the risk of death by 35% in patients with relapse during or after docetaxel-based therapy.
The advent of new agents for the management of advanced CRPC has increased the choices for patients whose options were limited. Additional experience will determine the optimal sequencing of these agents, their roles in combination therapy, and their activity in patients with earlier disease.
回顾三种新批准用于治疗晚期去势抵抗性前列腺癌(CRPC)的药物的活性:sipuleucel-T、卡巴他赛和醋酸阿比特龙。
通过 MEDLINE(1977 年至 2012 年 6 月)和美国临床肿瘤学会(2000 年至 2012 年)的摘要检索文献,使用术语去势抵抗性和激素难治性前列腺癌、sipuleucel-T、卡巴他赛、阿比特龙、Provenge、Jevtana 和 Zytiga。还回顾了从出版物中确定的参考文献。
评估了从英语来源的人类研究中确定的文章。
对于 CRPC 患者的选择有限,对于那些失败或不能耐受基于多西紫杉醇的治疗的患者几乎没有提供什么。三种新的药物,具有非常不同的作用机制,改变了这一点,无疑也改变了这些患者的治疗模式。每种药物都证明对患者的生存有影响。Sipuleucel-T,第一种批准用于治疗 CRPC 的免疫疗法,在一项安慰剂对照的无症状患者试验中,将中位总生存期延长了 4.1 个月,降低了 22%的死亡风险。Sipuleucel-T 可在基于多西紫杉醇的治疗之前给予。卡巴他赛,一种紫杉烷化疗药物,在一项 3 期试验中,在基于多西紫杉醇的治疗期间或之后癌症进展的患者中,将中位总生存期延长了 2.4 个月,降低了 30%的死亡风险。醋酸阿比特龙,一种激素治疗药物,在基于多西紫杉醇的治疗期间或之后复发的患者中,将中位总生存期延长了 3.9 个月,降低了 35%的死亡风险。
新的药物用于治疗晚期 CRPC 的出现增加了那些选择有限的患者的选择。更多的经验将确定这些药物的最佳顺序、它们在联合治疗中的作用以及它们在早期疾病患者中的活性。