我国Ⅰ类抗肿瘤靶向药物剂量选择策略及现状分析  

Strategy and current situation analysis for dose selection of novel anti-cancer drugs in China

作　　者：朱仲玲 余俊 ZHU Zhong-ling;YU Jun(GCP Office,Tianjin Medical University Cancer Institute&Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院国家药物临床试验机构办公室/国家恶性肿瘤临床医学研究中心/天津市恶性肿瘤临床医学研究中心/天津市肿瘤防治重点实验室,天津300060

出　　处：《中国新药杂志》2024年第23期2417-2425,共9页Chinese Journal of New Drugs

基　　金：天津市医学重点学科(专科)建设项目(TJYXZDXK-009A)。

摘　　要：目的:描述和分析2018—2023年国家药品监督管理局首次批准上市的国产Ⅰ类抗肿瘤靶向药物剂量发现和选择策略。方法:通过收集国家药品监督管理局药品审评中心公布的药品审评报告、药品说明书以及所有药品上市前研究数据,梳理国产Ⅰ类抗肿瘤靶向药物的剂量选择策略。结果:42款国产Ⅰ类抗肿瘤靶向药物中仅10款在Ⅰ期临床试验阶段确定了最大耐受剂量,32款说明书用量低于最大耐受剂量(maximum tolerated dose,MTD)或最大给药剂量。除了Ⅰa期剂量递增临床研究外,所有药物在剂量探索阶段均开展了1个或多个剂量的扩展研究。结论:MTD不再是大多数新型抗肿瘤靶向药物剂量选择的主要依据,最佳给药策略是基于临床药理学研究结果的综合评估。Objective:To describe and analyze the dose discovery and selection strategies for domestically produced classⅠanti-tumor targeted new drugs approved by the National Medical Products Administration from 2018 to 2023.Methods:By collecting drug evaluation reports,drug instructions,and all pre-market studies of drugs released by the Drug Evaluation Center of the National Medical Products Administration,the dosage selection strategies for ClassⅠanti-tumor targeted new drugs were sorted out.Results:Among the 42 domestically produced ClassⅠanti-tumor targeted drugs,10 were identified the maximum tolerable dose in the phase I clinical trials and 32 drugs were approved at a dose lower than the maximum tolerable dose or maximum administration dose.One or more dose expansion studies were conducted for all drugs beyond the dose-escalation studies.Conclusion:MTD is no longer the main basis for dose selection of most targeted anticancer drugs.The optimal dosing strategy is based on a comprehensive evaluation of clinical pharmacology results.

关 键 词：抗肿瘤靶向药物 剂量选择 最大耐受剂量 最佳剂量 

分 类 号：R979.1[医药卫生—药品]