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转移性去势抵抗性前列腺癌治疗中的当代药物

Contemporary agents in the management of metastatic castration-resistant prostate cancer.

作者信息

Kapoor Anil, Wu Christopher, Shayegan Bobby, Rybak Adrian P

机构信息

McMaster Institute of Urology, Division of Urology, Department of Surgery, McMaster University, Hamilton, ON, Canada; St. Joseph's Hospital, Hamilton, ON, Canada.

出版信息

Can Urol Assoc J. 2016 Nov-Dec;10(11-12):E414-E423. doi: 10.5489/cuaj.4112. Epub 2016 Dec 12.

Abstract

Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC. Cabazitaxel, abiraterone acetate, and enzalutamide are three agents recently approved for the treatment of mCRPC, having shown overall survival benefit in patients previously treated with docetaxel, while both abiraterone acetate and enzalutamide have also shown promise in the pre-docetaxel setting. Sipuleucel-T has shown overall survival benefit in asymptomatic mCRPC, while radium-223 provides survival benefit to patients with mCRPC who are symptomatic from their skeletal metastases in both docetaxel-naïve patients and post-docetaxel patients. Denosumab, an anti-RANKL antibody, has been approved for the prevention of skeletal-related events in patients with prostate cancer bone metastases. This review examines the phase 3 trials supporting the use of theses novel agents in the treatment of mCRPC. While these agents provide incremental increases in patient survival, further study to determine the best choice, combination, and/or sequencing of administration is still necessary.

摘要

自2004年以来,以多西他赛为基础的化疗一直是转移性去势抵抗性前列腺癌(mCRPC)的标准治疗方案。在过去几年中,这种疾病的治疗格局发生了重大的模式转变。对前列腺癌生物学的更深入理解,以及新型药物的开发,为治疗未经化疗和耐药的疾病带来了希望。在多西他赛被用作mCRPC的一线治疗方案之后,五种新型疗法已在mCRPC中显示出生存获益。卡巴他赛、醋酸阿比特龙和恩杂鲁胺是最近被批准用于治疗mCRPC的三种药物,它们在先前接受多西他赛治疗的患者中显示出总生存获益,而醋酸阿比特龙和恩杂鲁胺在多西他赛治疗前的情况下也显示出前景。西妥昔单抗在无症状的mCRPC中显示出总生存获益,而镭-223为在多西他赛初治患者和多西他赛治疗后患者中因骨转移出现症状的mCRPC患者提供生存获益。地诺单抗,一种抗RANKL抗体,已被批准用于预防前列腺癌骨转移患者的骨相关事件。本综述考察了支持这些新型药物用于治疗mCRPC的3期试验。虽然这些药物能逐步提高患者生存率,但仍有必要进一步研究以确定最佳选择、联合用药和/或给药顺序。

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