背景:在临床实践中,干血斑点(DBS)采样是全血采样的便捷替代方法,用于治疗药物监测(TDM)。这项研究的目的是系统地回顾已经检查并使用DBS采样进行化疗和靶向治疗剂治疗实体癌患者的TDM的研究。
方法:使用PRISMA指南,对EMBASE和PUBMED进行了系统的文献检索,以确定使用DBS采样监测化疗或靶向治疗治疗实体癌的合格临床研究.
结果:在23项符合条件的研究中,3通过DBS和全血测定的药物浓度之间的测量一致性,7种已开发的DBS分析方法,13人同时表演。DBS用于依维莫司的TDM(3项研究),vemurafenib(2项研究),帕唑帕尼(2项研究),阿比特龙(2项研究),米托坦,伊马替尼,adavosertib,卡培他滨,5-氟尿嘧啶,吉西他滨,环磷酰胺,异环磷酰胺,依托泊苷,伊立替康,多西他赛,吉非替尼,palbociclib/ribociclib,和紫杉醇(各一项研究)。研究包括14名参与者(范围:6-34),将10-50μL的血液分配在DBS卡(20)和Mitra装置(3)上。使用DBS的20项研究中有17项发现,在正常血细胞比容范围内,血细胞比容对所开发方法的准确性和精密度没有显着影响(例如,29.0%-59.0%)。DBS与血浆或静脉浓度高度相关(相关系数,0.872-0.999)适用于所有药物,除了米托坦,不满足预定义的显著性水平(r>0.872;相关系数,r=0.87,P<0.0001)。
结论:DBS为许多抗癌药物的TDM提供了一种替代取样策略。需要进一步研究,以建立用于采样和处理DBS样品的标准化方法,以便将来实施。
Dried blood spot (DBS) sampling is a convenient alternative to whole-blood sampling for therapeutic drug monitoring (TDM) in clinical practice. The aim of this study was to systematically
review studies that have examined and used DBS sampling for the TDM of chemotherapy and targeted therapy agents for the treatment of patients with solid cancers.
Using the PRISMA guidelines, a systematic literature search of EMBASE and PUBMED was performed to identify eligible clinical studies that used DBS sampling to monitor chemotherapy or targeted therapy for the treatment of solid cancers.
Of the 23 eligible studies, 3 measured concordance between drug concentrations determined by DBS and whole-blood, 7 developed analytical methods of DBS, and 13 performed both. DBS was employed for the TDM of everolimus (3 studies), vemurafenib (2 studies), pazopanib (2 studies), abiraterone (2 studies),
mitotane, imatinib, adavosertib, capecitabine, 5-fluorouracil, gemcitabine, cyclophosphamide, ifosfamide, etoposide, irinotecan, docetaxel, gefitinib, palbociclib/ribociclib, and paclitaxel (one study each). The studies included a median of 14 participants (range: 6-34), with 10-50 μL of blood dispensed on DBS cards (20) and Mitra devices (3). Seventeen of the 20 studies that used DBS found no significant impact of the hematocrit on the accuracy and precision of the developed method in the normal hematocrit ranges (eg, 29.0%-59.0%). DBS and plasma or venous concentrations were highly correlated (correlation coefficient, 0.872-0.999) for all drugs, except
mitotane, which did not meet a predefined level of significance (r > 0.872; correlation coefficient, r = 0.87, P < 0.0001).
DBS provides an alternative sampling strategy for the TDM of many anticancer drugs. Further research is required to establish a standardized approach for sampling and processing DBS samples to allow future implementation.