达沙替尼联合化疗治疗儿童费城染色体阳性急性淋巴细胞白血病的循证药学评价

Evidence-Based Pharmacy Evaluation of Dasatinib Plus Intensive Chemotherapy in the Therapy of Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

目的全面评价达沙替尼在儿童费城染色体阳性(Ph^(+))急性淋巴细胞白血病(ALL)中的应用情况,为临床合理应用提供循证证据。方法检索Daily Med、EMC药品信息数据库及药品说明书,收集达沙替尼的最新版说明书并比较不同厂家说明书内容的差异性;检索美国国立综合癌症网络(NCCN)、美国国家癌症研究所(NCI)、医脉通、UpToDate等网站,收集达沙替尼治疗儿童Ph^(+)ALL的诊疗指南/规范并对推荐的治疗方案进行归纳总结;计算机检索PubMed、Embase、Cochrane Library、Clinical Trials.gov、CNKI、Sino-Med、VIP和万方数据库,检索时限为2000年1月1日至2023年3月31日,收集达沙替尼治疗儿童Ph^(+)ALL的临床试验研究并进行meta分析。结果共获得4个厂家的21条药品标签信息,不同厂家说明书承载内容各异,达沙替尼原研说明书信息最规范、全面,国产达沙替尼说明书未记载治疗儿童Ph^(+)ALL的适应证;收集到儿童ALL诊疗指南/规范3篇,其中2篇推荐达沙替尼联合化疗可一线治疗Ph^(+)ALL;检索到达沙替尼治疗儿童Ph^(+)ALL的研究文献186篇,经逐层筛选,最终4篇文献289例Ph^(+)ALL患儿纳入单臂meta分析。结论达沙替尼联合化疗治疗儿童Ph^(+)ALL在国内属于超说明书用药,该联合治疗方案是否能带来临床获益,仍需大规模的真实世界数据和更长的随访时间来确证。

Objective To provide evidence-based support for clinicians,a systemic review was conducted to evaluate the safety and efficacy of dasatinib in the treatment of children with Philadelphia chromosomal positive(Ph^(+))acute lymphoblastic leukemia(ALL).Methods The latest version of dasatinib label was obtained through searching Daily Med,EMC databases and drug packaging,and the differences in the contents of different manufacturers were evaluated.The websites,such as the National Comprehensive Cancer Network(NCCN),the National Cancer Institute(NCI),Yimaitong and UpToDate were searched and the related practice guidelines/norms were retrieved and summrized.PubMed,Embase,Cochrane Library,Clinical Trials.gov,CNKI,CBM,VIP and Wanfang Data from January 1,2000 to March 31,2023 were searched,and all literatures involved dasatinib in treatment of children with Ph^(+)ALL were retrieved,and the meta-analysis was performed.Results A total of 21 drug labels from 4 manufacturers were obtained.Only the original manufacturer’s label of dasatinib was the most standardized and comprehensive,and the domestic dasatinib didn’t approve the indication for treatment in pediatric population with Ph^(+)ALL.Three guidelines/norms were obtained,and two of which explicitly recommended dasatinib combined with chemotherapy as the first-line treatment for Ph^(+)ALL.A total of 186 studies were retrieved,4 literatures involved 289 children with Ph^(+)ALL were included in the single-arm meta-analysis.Conclusion Dasatinib combined with chemotherapy for treatment in children with Ph^(+)ALL is an off-label drug use in China.Whether the combination therapy could brought clinical benefits,a large-scale real world clinical data and more longer follow-up time would be need.