Pyrgidis Nikolaos, Vakalopoulos Ioannis, Sountoulides Petros
1st Department of Urology, Aristotle University of Thessaloniki, 15-17 Agiou Evgeniou Street, TK 55133, Thessaloniki, Greece.
Hormones (Athens). 2021 Mar;20(1):73-84. doi: 10.1007/s42000-020-00251-5. Epub 2020 Nov 2.
Prostate cancer (PCa) is the commonest non-cutaneous malignancy worldwide and the second cause of cancer death among males in the USA. Approval of the new androgen receptor axis-targeted (ARAT) agents (abiraterone acetate, enzalutamide, apalutamide, and darolutamide) has altered the course of advanced PCa. We aimed to assess the endocrine and metabolic adverse events associated with treatment using ARAT compounds.
We searched the PubMed, Cochrane Library, and Scopus databases from database inception to August 2020. We included randomized controlled trials reporting the endocrine and metabolic side effects of ARAT agents compared to each other or to placebo.
Although metastatic PCa remains incurable, ARAT medications combined with androgen deprivation therapy improve overall metastasis-free and progression-free survival in metastatic hormone-sensitive PCa, non-metastatic castration-resistant PCa, and metastatic castration-resistant PCa patients. This benefit comes at the cost of certain endocrine and metabolic consequences. Treatment with abiraterone acetate induces mineralocorticoid excess, hypokalemia, hypertension, elevated liver function tests, insulin resistance, and hyperglycemia. Enzalutamide may induce or worsen hypertension and increase the risk of falls and fractures in elderly patients, while common endocrine adverse events of apalutamide include hypothyroidism, hypertension, and skin rash. On the other hand, darolutamide seems to have a somewhat safer endocrine and metabolic profile.
Treatment of advanced PCa should be personalized, with administration of a combination of androgen deprivation therapy, ARAT agents, and chemotherapy being based on the patient's safety profile and the risk of side effects.
前列腺癌（PCa）是全球最常见的非皮肤恶性肿瘤，也是美国男性癌症死亡的第二大原因。新型雄激素受体轴靶向（ARAT）药物（醋酸阿比特龙、恩杂鲁胺、阿帕他胺和达罗他胺）的获批改变了晚期PCa的治疗进程。我们旨在评估使用ARAT化合物治疗相关的内分泌和代谢不良事件。
我们检索了从数据库建立至2020年8月的PubMed、Cochrane图书馆和Scopus数据库。我们纳入了报告ARAT药物与彼此或安慰剂相比的内分泌和代谢副作用的随机对照试验。
尽管转移性PCa仍然无法治愈，但ARAT药物联合雄激素剥夺疗法可改善转移性激素敏感性PCa、非转移性去势抵抗性PCa和转移性去势抵抗性PCa患者的无转移和无进展总生存期。这种益处是以某些内分泌和代谢后果为代价的。醋酸阿比特龙治疗会导致盐皮质激素过多、低钾血症、高血压、肝功能检查升高、胰岛素抵抗和高血糖。恩杂鲁胺可能会诱发或加重高血压，并增加老年患者跌倒和骨折的风险，而阿帕他胺常见的内分泌不良事件包括甲状腺功能减退、高血压和皮疹。另一方面，达罗他胺似乎具有相对更安全的内分泌和代谢特征。
晚期PCa的治疗应个性化，雄激素剥夺疗法、ARAT药物和化疗的联合应用应基于患者的安全性和副作用风险。
