Traboulsi Samer L, Saad Fred
Division of Urology, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
Curr Opin Support Palliat Care. 2017 Sep;11(3):216-224. doi: 10.1097/SPC.0000000000000280.
Bone-targeted agents (BTAs), such as zoledronic acid and denosumab, delay the occurrence of skeletal-related events (SREs) in metastatic prostate cancer (PCa) patients. Recently, several agents, such as abiraterone acetate, enzalutamide and radium-223, were approved for the treatment of metastatic castration-resistant PCa (mCRPC). These agents resulted in improved overall survival (OS), pain control and had positive effects on bone health. Combining BTAs to the newly approved agents demonstrates additional benefits that warrant a review of available evidence looking at appropriate combination therapies and timing of BTAs for optimizing the management of advanced and metastatic PCa.
Post-hoc analyses of randomized trials demonstrated some benefits from combination therapy, such as increased OS when denosumab was used concurrently with radium-223 and when BTAs were used with abiraterone acetate. BTAs were not beneficial for the prevention of bone metastases.
There is a suggestion of synergy or additive effects between BTAs and new agents approved for the treatment of metastatic PCa, resulting in potential clinical benefits. Therefore, prospective randomized studies evaluating the safety and benefits of combination therapies to address gaps in the literature are needed to optimize treatment of mCRPC.
骨靶向药物（BTAs），如唑来膦酸和地诺单抗，可延缓转移性前列腺癌（PCa）患者骨骼相关事件（SREs）的发生。最近，几种药物，如醋酸阿比特龙、恩杂鲁胺和镭-223，被批准用于治疗转移性去势抵抗性PCa（mCRPC）。这些药物提高了总生存期（OS），控制了疼痛，并对骨骼健康有积极影响。将BTAs与新批准的药物联合使用显示出额外的益处，这值得回顾现有证据，探讨合适的联合治疗方法以及BTAs的使用时机，以优化晚期和转移性PCa的管理。
随机试验的事后分析表明联合治疗有一些益处，如地诺单抗与镭-223同时使用以及BTAs与醋酸阿比特龙联用时OS增加。BTAs对预防骨转移无益。
BTAs与批准用于治疗转移性PCa的新药物之间存在协同或相加作用，从而产生潜在的临床益处。因此，需要进行前瞻性随机研究来评估联合治疗的安全性和益处，以填补文献中的空白，从而优化mCRPC的治疗。
