@article{APS11113,
author = {Hao-ran Dai and Yang Yang and Chen-yu Wang and Yue-ting Chen and Yi-fan Cui and Pei-jing Li and Jia Chen and Chen Yang and Zheng Jiao},
title = {Trilaciclib dosage in Chinese patients with extensive-stage small cell lung cancer: a pooled pharmacometrics analysis},
journal = {Acta Pharmacologica Sinica},
volume = {45},
number = {10},
year = {2024},
keywords = {},
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 280 mg/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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11113}
}