DPYD基因多态性检测在氟尿嘧啶化疗中安全性、经济性快速卫生技术评估

Safety and Economy of Fluorouracil Chemotherapy with DPYD Gene Polymorphism Detection: A Rapid Health Technology Assessment

目的 通过快速卫生技术评估(health technology assessment, HTA)的方法,评价在接受氟尿嘧啶化疗前进行二氢嘧啶脱氢酶(dihydropyrimidine dehydrogenase,DPYD)基因检测的有效性、安全性和经济性,考察基于基因检测实施氟尿嘧啶个体化药物治疗的必要性,为临床医生和决策者提供高效、便捷的循证依据。方法 检索Pubmed, the Cochrane Library,万方和中国知网等数据库。有2位研究者根据纳入与排除标准独立筛选文献、提取资料和评价质量后,对结果进行定性分析。结果 本研究共纳入HTA1篇、系统评价/Meta分析5篇以及药物经济学研究5篇。结果显示,DYPD*2A、2846A>T、*13和1236G>A基因突变患者不良反应发生率显著高于野生型(P<0.05)。在接受氟尿嘧啶化疗前进行DPYD基因检测并采用基因型指导给药能够显著降低患者的不良反应同时减少治疗成本。结论 对于应用氟尿嘧啶类药物为基础化疗的肿瘤患者,建议用药前进行DPYD基因型检测,若患者发生基因突变,建议适当减少给药剂量或换用其他药物,未来有必要在国内开展经济学研究。

OBJECTIVE To evaluate the efficacy,safety,and economy of dihydropyrimidine dehydrogenase(DPYD)gene testing before chemotherapy with fluorouracil by rapid health technology assessment(HTA)and investigate the necessity of individualized fluorouracil therapy based on genetic testing and provide efficient and convenient evidence-based evidence for clinicians and policymakers.METHODS PubMed,the Cochrane Library,Wanfang,CNKI and other databases were searched,two researchers independently screened the literature,extracted data,and evaluated the quality according to inclusion and exclusion criteria,and conducted qualitative analysis of the results.RESULTS A total of 1HTA,5 systematic reviews/meta-analyses and 5pharmacoeconomic studies were included.The results showed that the incidence of adverse reactions in patients with DYPD*2A,2846A>T,*13 and 1236G>A gene mutations was significantly higher than that in wild type(P<0.05).DPYD gene testing and genotype-guided administration before chemotherapy with fluorouracil could significantly reduce patients′adverse reactions and reduce treatment costs.CONCLUSION For cancer patients with fluorouracil-based chemotherapy,DPYD genotype testing is recommended before medication.If patients have gene mutations,it is recommended to appropriately reduce the dose or switch to other drugs.It is necessary to carry out economic research in China in the future.