骨肉瘤患者大剂量甲氨蝶呤血药峰浓度与临床结局相关性的系统评价  

Association between high-dose methotrexate serum peak concentrations and clinical outcomes in osteosarcoma: a systematic review

作　　者：宋再伟 黄振城 张恩瑶 刘爽 谈志远 赵荣生[1,2] SONG Zai-wei;HUANG Zhen-cheng;ZHANG En-yao;LIU Shuang;TAN Zhi-yuan;ZHAO Rong-sheng(Department of Pharmacy,Peking University Third Hospital,Beijing 100191,China;Institute for Drug Evaluation,Peking University Health Science Center,Beijing 100191,China;Department of Pharmacy Administration and Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University,Beijing 100191,China)

机构地区：[1]北京大学第三医院药剂科,北京100191 [2]北京大学医学部药物评价中心,北京100191,北京100191 [3]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国临床药理学杂志》2019年第22期2907-2910,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划“纳米科技”重点专项基金资助项目(2017YFA0205600)

摘　　要：目的系统评价骨肉瘤患者大剂量甲氨蝶呤血药峰浓度与临床结局的相关性。方法计算机系统检索MEDLINE(Ovid)、EMBASE(Ovid)、中国期刊全文数据库(CNKI)、万方数字化期刊全文数据库(Wan Fang Database)和中国生物医学文献数据库(CBM),补充检索Clinical Trials.gov,检索均从建库至2018年3月,并手工补充检索纳入文献的参考文献。2名作者独立筛选文献、提取数据,用NOS(Newcastle-Ottawa Scale)量表独立进行质量评价后,对相关结局指标进行描述性分析。结果纳入6篇研究,共878例骨肉瘤患者,6篇研究NOS均分8.20。6篇研究报道了血药峰浓度与临床疗效的相关性,其中5篇研究结论提示了血药峰浓度目标值与大剂量甲氨蝶呤临床疗效存在显著相关性。Cmax≥500μmol·L^-1与更长的无病生存期(DFS)相关(P<0.05),但与总生存期(OS)无显著相关性(P>0.05);Cmax≥700μmol·L^-1与更高的组织学完全反应率、组织学良好反应率、更低的复发率相关(P<0.05);Cmax≥1000μmol·L^-1与更好的10年DFS相关(P<0.05),但与组织学反应之间无显著相关性(P>0.05);与Cmax<1500μmol·L^-1相比,Cmax≥1500μmol·L^-1时5年无事件生存期(EFS)比例更低(P<0.05)。暂无队列研究评价血药峰浓度与安全性结局的相关性。结论骨肉瘤患者中大剂量甲氨蝶呤Cmax在10001500μmol·L^-1可能有助于实现更有效的临床预后。Objective To systematically review the possible association between high-dose methotrexate serum peak concentrations and clinical outcomes in patients with osteosarcoma through evidence-based methods.Methods Databases including MEDLINE(Ovid),EMBASE(Ovid),Clinical Trials.gov,CNKI,Wanfang Database,and CBM were searched from inceptions to March 2018.Manual search of references in relevant literatures was also performed.Two reviewers independently screened records to identify eligible studies,extracted data and assessed their qualities under Newcastle-Ottawa scale(NOS).Finally outcomes were integrated and analyzed by qualitative analysis.Results Totally six studies(878 patients with osteosarcoma)were included and earned 8.20 NOS points on average.Six studies reported efficacy outcomes,five of which showed dramatic correlation between peak serum concentrations and efficacy outcomes.Cmax≥500μmol·L^-1 was correlated with longerdisease-free survival(DFS)(P<0.05),but was not associated with overall surrival(OS)(P>0.05).Cmax≥700μmol·L^-1 was correlated with better histological response and lower recurrence rate(P<0.05).Cmax≥1000μmol·L^-1 was correlated with better 10 year-DFS(P<0.05),but was not associated with histological response(P>0.05).Cmax≥1500μmol·L^-1 was correlated with worse 5 year-event-free survival(EFS)(P<0.05).Currently none of cohort studies evaluated the association between peak serum concentration and safety outcomes.Conclusion For patients with osteosarcoma,peak serum concentration between 1000μmol·L^-1 and 1500μmol·L^-1 might contribute to better efficacy.

关 键 词：大剂量甲氨蝶呤 骨肉瘤 峰浓度 临床结局 系统评价 

分 类 号：R979.1[医药卫生—药品]