曲拉西利用于骨髓保护的作用机制及临床研究进展

Mechanism of action and clinical research progress of trilaciclib in bone marrow protection

骨髓抑制(chemotherapy-induced myelosupression,CIM)是化疗药物最常见的毒性反应,80%以上的化疗药物都会导致CIM。CIM通常表现为中性粒细胞、血小板及红细胞减少等。CIM会导致化疗药物减量、延迟给药,严重影响肿瘤患者的生活质量,降低化疗的整体抗肿瘤效果。作为全球首个具有全系骨髓保护作用的药物,曲拉西利是一种高效、选择性、可逆的细胞周期蛋白依赖性激酶(cyclin-dependent kinase,CDK)4/6抑制剂,可将造血干细胞和祖细胞、免疫细胞等细胞周期短暂阻滞在DNA合成前期(G1期),以降低化疗引起的损伤,从而发挥骨髓保护及免疫调节的作用。2021年4月,曲拉西利在美国获批上市。2022年7月,曲拉西利在我国获批上市,首个获批适应证为“适用于既往未接受过系统性化疗的广泛期小细胞肺癌患者,在接受含铂类药物联合依托泊苷方案治疗前预防性给药,以降低化疗引起的CIM的发生率”。本文拟对曲拉西利的作用机制、药动学、药物相互作用机制、临床评价及安全性等相关研究进展进行系统阐述,以期为临床实践提供进一步的参考及依据。

Chemotherapy⁃induced myelosupression(CIM)is the most common toxicity of chemotherapy drugs.Usually,more than 80%of chemotherapy drugs lead to myelosuppression,and CIM is usually characterized by neutropenia,thrombocytopenia and erythrocytopenia.Dose reduction and delayed administration of chemotherapy drugs by CIM seriously reduce the life quality of patients and the overall anti⁃tumor effect of chemotherapy.As the first drug approved for bone marrow protection,trilaciclib is a highly effective,selective and reversible cyclin⁃dependent kinase(CDK)4/6 inhibitor,which can temporarily block cell cycle of hematopoietic stem/progenitor cells and immune cells in G1 phase,so as to reduce the damage caused by chemotherapy and protect bone marrow protection.In April 2021,trilaciclib was approved by FDA as a myelo preservation in the United States.In July 2022,trilaciclib was approved by the National Medical Products Administration for marketing in China,and the first indication of trilaciclib in China was for patients with extensive stage small⁃cell lung cancer. In this review, themechanisms of action, pharmacokinetics, drug interaction mechanism, clinical evaluation, safety and other relatedresearch progress of trilaciclib are systematically reviewed, aiming to provide further reference and basis for clinicalpractice.