Buchler Tomas
Department of Oncology, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06, Prague, Czech Republic.
Target Oncol. 2025 May 16. doi: 10.1007/s11523-025-01150-8.
Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, has been established as an effective androgen deprivation therapy (ADT) for advanced prostate cancer, offering advantages over traditional GnRH agonists. The combination of relugolix with androgen receptor pathway inhibitors (ARPIs) is increasingly utilized in clinical practice, necessitating an understanding of its pharmacokinetics, efficacy, safety, and drug-drug interactions. This review explores the real-world data and clinical studies evaluating relugolix coadministration with ARPIs, including enzalutamide, abiraterone, apalutamide, and darolutamide. Pharmacokinetic interactions, particularly via the CYP3A4 enzyme system and P-glycoprotein (P-gp) transporter, influence drug exposure and, in theory, necessitate dose adjustments in certain combinations. However, clinical studies and real-world studies suggest that relugolix maintains testosterone suppression when combined with ARPIs even if administered in a standard dose. While these findings support the efficacy and safety of relugolix-based combination therapy, further large-scale prospective trials are needed to refine treatment recommendations and provide information on long-term outcomes.
Relugolix是一种口服促性腺激素释放激素（GnRH）受体拮抗剂，已被确立为晚期前列腺癌的有效雄激素剥夺疗法（ADT），相较于传统的GnRH激动剂具有优势。Relugolix与雄激素受体通路抑制剂（ARPI）联合使用在临床实践中越来越普遍，因此有必要了解其药代动力学、疗效、安全性及药物相互作用。本综述探讨了评估Relugolix与ARPI（包括恩杂鲁胺、阿比特龙、阿帕他胺和达罗他胺）联合使用的真实世界数据和临床研究。药代动力学相互作用，尤其是通过细胞色素P450 3A4（CYP3A4）酶系统和P-糖蛋白（P-gp）转运体的相互作用，会影响药物暴露，理论上某些联合用药需要调整剂量。然而，临床研究和真实世界研究表明，Relugolix与ARPI联合使用时，即使采用标准剂量给药，也能维持睾酮抑制作用。虽然这些发现支持了基于Relugolix的联合治疗的疗效和安全性，但仍需要进一步的大规模前瞻性试验来完善治疗建议并提供长期预后信息。
