Division of Medical OncologyDepartment of Oncology, University of Turin, San Luigi Gonzaga Hospital, Turin, Italy.
Division of Medical OncologyDepartment of Oncology, University of Turin, San Luigi Gonzaga Hospital, Turin, Italy
Endocr Relat Cancer. 2018 Jan;25(1):R1-R9. doi: 10.1530/ERC-17-0355. Epub 2017 Sep 28.
Antiandrogen withdrawal syndrome is an unpredictable event diagnosed in patients with hormone-sensitive prostate cancer treated with combined androgen blockade therapy. It is defined by prostate-specific antigen value reduction, occasionally associated with a radiological response, that occurs 4-6 weeks after first-generation antiandrogen therapy discontinuation. New-generation hormonal therapies, such as enzalutamide and abiraterone acetate, improved the overall survival in patients with metastatic castration-resistant prostate cancer, and recent trials have also shown the efficacy of abiraterone in hormone-sensitive disease. In the last few years, several case reports and retrospective studies suggested that the withdrawal syndrome may also occur with these new drugs. This review summarizes literature data and hypothesis about the biological rationale underlying the syndrome and its potential clinical relevance, focusing mainly on new-generation hormonal therapies. Several studies suggest that androgen receptor gain-of-function mutations are involved in this syndrome, shifting the antiandrogen activity from antagonist to agonist. Several different drug-specific point mutations have been reported. The association of the withdrawal syndrome for enzalutamide and abiraterone needs confirmation by additional investigations. However, new-generation hormonal therapies being increasingly used in all stages of disease, more patients may experience the syndrome when stopping the treatment at the time of disease progression, although the clinical relevance of this phenomenon in the management of metastatic castration-resistant prostate cancer remains to be defined.
雄激素撤退综合征是一种不可预测的事件，发生于接受联合雄激素阻断治疗的激素敏感前列腺癌患者中。其定义为前列腺特异性抗原值降低，偶尔伴有影像学反应，发生于第一代抗雄激素治疗停药后 4-6 周。新一代激素治疗药物，如恩扎卢胺和醋酸阿比特龙，改善了转移性去势抵抗性前列腺癌患者的总生存期，最近的试验也显示了醋酸阿比特龙在激素敏感疾病中的疗效。在过去几年中，一些病例报告和回顾性研究表明，该综合征也可能发生在这些新药物中。这篇综述总结了关于该综合征潜在生物学基础及其潜在临床意义的文献数据和假说，主要集中在新一代激素治疗药物上。一些研究表明，雄激素受体获得性功能突变参与了该综合征，使抗雄激素活性从拮抗剂转变为激动剂。已经报道了几种不同的药物特异性点突变。恩扎卢胺和醋酸阿比特龙撤退综合征的相关性需要通过进一步的研究来证实。然而，随着新一代激素治疗药物在疾病各个阶段的广泛应用，更多的患者在疾病进展时停止治疗时可能会经历该综合征，尽管这种现象在转移性去势抵抗性前列腺癌的治疗管理中的临床意义仍有待确定。
