Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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新的雄激素受体轴靶向药物治疗晚期前列腺癌的内分泌后果

目的

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。新的雄激素受体轴靶向 (ARAT) 药物（醋酸阿比特龙、恩杂鲁胺、阿帕鲁胺和达洛鲁胺）的批准改变了晚期 PCa 的病程。我们旨在评估与使用 ARAT 化合物治疗相关的内分泌和代谢不良事件。

方法

我们检索了从数据库开始到 2020 年 8 月的 PubMed、Cochrane 图书馆和 Scopus 数据库。我们纳入了随机对照试验，这些试验报告了 ARAT 药物与其他药物或安慰剂相比的内分泌和代谢副作用。

结果

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 患者的总体无转移和无进展生存期。这种好处是以某些内分泌和代谢后果为代价的。用醋酸阿比特龙治疗会导致盐皮质激素过量、低钾血症、高血压、肝功能检查升高、胰岛素抵抗和高血糖。恩杂鲁胺可能诱发或加重老年患者的高血压并增加跌倒和骨折的风险，而阿帕鲁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，darolutamide 似乎具有更安全的内分泌和代谢特征。

结论

晚期 PCa 的治疗应个体化，根据患者的安全状况和副作用风险联合使用雄激素剥夺疗法、ARAT 药物和化疗。