Karthaus Meinolf, Lehrnbecher Thomas, Lipp Hans-Peter, Kluge Stefan, Buchheidt Dieter
Medical Clinic IV, Hematology and Oncology, Neuperlach Hospital, Munich, Germany,
Ann Hematol. 2015 Apr;94(4):547-56. doi: 10.1007/s00277-015-2333-z. Epub 2015 Feb 20.
Invasive aspergillosis (IA) is a life-threatening complication in hematological cancer patients. Voriconazole (VCZ) is the established first-line treatment of IA. VCZ has a nonlinear pharmacokinetic profile and exhibits considerable variability of drug exposure. Therefore, therapeutic drug monitoring (TDM) of VCZ may help to improve treatment results in IA patients, but evidence-based data on the clinical use of TDM in patients treated with VCZ for IA are scarce. Evidence-based guidance is needed to support decisions on the use of TDM in routine VCZ therapy of IA. Our present analysis assessed published studies for evidence-based criteria for TDM of VCZ to improve efficacy and safety of IA therapy in cancer patients. Literature searches of MEDLINE and Cochrane database were performed. We identified 27 clinical studies reporting on the use of plasma level monitoring and/or TDM for VCZ. For each study, strength of recommendation and quality of evidence were categorized according to predefined criteria. A number of studies were published on plasma level monitoring (PLM) and TDM in VCZ therapy of IA. Across studies, VCZ levels >5-5.5 mg/L were found to be associated with toxicity, while reaching minimum levels of >1-2 mg/L appeared to improve efficacy. Timing, frequency, and intervention thresholds and dosage increments of VCZ for adjustment of plasma levels remain to be established. Currently, there is still no conclusive evidence for recommendations in routine clinical practice. More data from prospective randomized studies with TDM are desirable to provide a solid evidence basis for these approaches.
侵袭性曲霉病（IA）是血液系统癌症患者中一种危及生命的并发症。伏立康唑（VCZ）是IA既定的一线治疗药物。VCZ具有非线性药代动力学特征，药物暴露存在显著变异性。因此，VCZ的治疗药物监测（TDM）可能有助于改善IA患者的治疗效果，但关于TDM在接受VCZ治疗的IA患者临床应用的循证数据稀缺。需要循证指南来支持IA常规VCZ治疗中TDM使用的决策。我们目前的分析评估了已发表的研究，以寻找基于循证的VCZ TDM标准，以提高癌症患者IA治疗的疗效和安全性。我们对MEDLINE和Cochrane数据库进行了文献检索。我们确定了27项报告VCZ血浆水平监测和/或TDM使用情况的临床研究。对于每项研究，根据预定义标准对推荐强度和证据质量进行分类。关于IA的VCZ治疗中的血浆水平监测（PLM）和TDM发表了多项研究。在各项研究中，发现VCZ水平>5 - 5.5mg/L与毒性相关，而达到>1 - 2mg/L的最低水平似乎可提高疗效。用于调整血浆水平的VCZ的时间、频率、干预阈值和剂量增量仍有待确定。目前，在常规临床实践中仍没有确凿的推荐证据。需要更多来自TDM前瞻性随机研究的数据，为这些方法提供坚实的循证基础。
