上海交通大学医学院Zheng Jiao团队近期取得重要工作进展，他们研究了Trilaciclib在中国广泛期小细胞肺癌患者中的用量：集合药物计量学分析。相关研究成果2024年5月17日在线发表于《中国药理学报》杂志上。

本研究旨在分析triraciclib在剂量-暴露-反应关系方面的潜在种族差异，triraciclib是一种静脉注射的细胞周期蛋白依赖性激酶4/6抑制剂，用于治疗广泛期小细胞肺癌（ES-SCLC）患者化疗诱导的骨髓抑制。

研究人员重点描述中国和非中国患者的这些关系，以进一步完善中国ES-SCLC患者的triraciclib给药方案。使用四项涉及中国和非中国ES-SCLC患者的随机2/3期试验的汇总数据进行群体药代动力学（PopPK）和暴露-反应（E–R）分析。PopPK分析显示，中国患者的triraciclib清除率比非中国ES-SCLC患者高出约17%。性别和体表面积影响了这两个人群中的triraciclib药物动力学，但没有产生显著的临床影响。E–R分析表明，随着剂量从200增加到280 mg /m²，无明显改变骨髓保护或抗肿瘤功效。

然而，在中国和非中国ES-SCLC患者中，输液部位反应、头痛和静脉炎/血栓性静脉炎的发生率随着triraciclib暴露量的增加而增加。这些发现表明，中国和非中国患者在剂量-暴露-反应关系方面没有显著的种族差异。这些研究结果支持在中国ES-SCLC患者中采用240 mg /m²静脉注射triraciclib的3天或5天给药方案。

附：英文原文

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

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

Issue&Volume: 2024-05-17

Abstract: 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 280mg/m2, 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/m2 intravenous 3-day or 5-day dosing regimen for trilaciclib in Chinese patients with ES-SCLC.

DOI: 10.1038/s41401-024-01297-6

Source: https://www.nature.com/articles/s41401-024-01297-6