Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer:a pooled pharmacometrics analysis  

作　　者：Hao-ran Dai Yang Yang Chen-yu Wang Yue-ting Chen Yi-fan Cui Pei-jing Li Jia Chen Chen Yang Zheng Jiao 

机构地区：[1]Department of Pharmacy,Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200030,China [2]Simcere Zaiming Pharmaceutical Co.Ltd.,Nanjing,210042,China

出　　处：《Acta Pharmacologica Sinica》2024年第10期2212-2225,共14页中国药理学报（英文版）

摘　　要：This study aimed to analyze potential ethnic disparities in the dose-exposure-response relationships of trilaciclib,a first-in-class intravenous cyclin-dependent kinase 4/6 inhibitor for treating chemotherapy-induced myelosuppression in patients with extensive-stage small cell lung cancer(ES-SCLC).This investigation focused on characterizing these relationships in both Chinese and non-Chinese patients to further refine the dosing regimen for trilaciclib in Chinese patients with ES-SCLC.Population pharmacokinetic(PopPK)and exposure-response(E-R)analyses were conducted using pooled data from four randomized phase 2/3 trials involving Chinese and non-Chinese patients with ES-SCLC.PopPK analysis revealed that trilaciclib clearance in Chinese patients was approximately 17%higher than that in non-Chinese patients with ES-SCLC.Sex and body surface area influenced trilaciclib pharmacokinetics in both populations but did not exert a significant clinical impact.E-R analysis demonstrated that trilaciclib exposure increased with a dosage escalation from 200 to 280 mg/m^(2),without notable changes in myeloprotective or antitumor efficacy.However,the incidence of infusion site reactions,headaches,and phlebitis/thrombophlebitis rose with increasing trilaciclib exposure in both Chinese and non-Chinese patients with ES-SCLC.These findings suggest no substantial ethnic disparities in the dose-exposure-response relationship between Chinese and non-Chinese patients.They support the adoption of a 240-mg/m^(2) intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

关 键 词：trilaciclib small cell lung carcinoma PHARMACOKINETICS population characteristics dose-response relationship ETHNICITY 

分 类 号：R734.2[医药卫生—肿瘤]