Doornhof K R, van der Linden P D, Boeke G M, Willemsen A E C A B, Daskapan A
Department of Clinical Pharmacy, Tergooi Medical Center, Hilversum, The Netherlands.
Department of Internal Medicine, Tergooi Medical Center, Hilversum, The Netherlands.
Eur J Clin Pharmacol. 2023 Apr;79(4):493-501. doi: 10.1007/s00228-023-03466-8. Epub 2023 Feb 9.
The primary objective of this study was to determine if dihydropyrimidine dehydrogenase (DPD) activity measured in peripheral blood mononuclear cells (PBMCs) is related to adverse events during fluoropyrimidine therapy.
A retrospective cohort study was conducted. The study population included 481 patients who received fluoropyrimidine treatment and for whom relevant patient characteristics were known and adverse events were noted in the electronic health records. Factors besides DPD phenotype that could affect the incidence of adverse events were corrected for using log regression. These log regression models were used to identify an association between the DPD phenotype measured in PBMCs and adverse events.
Patients with a decreased DPD activity measured in PBMCs suffered more adverse events. Results from log regression data show that this effect remains significant after correcting for dosage, chemotherapy regimen and relevant patient characteristics.
A significant correlation was found between reduced DPD enzyme activity in PBMCs and adverse events. The findings in this paper support further exploring DPD phenotyping as a method for preventing fluoropyrimidine-related adverse events. Further assessment of DPD phenotyping will require clinical validation in a prospective study.
本研究的主要目的是确定在外周血单核细胞（PBMCs）中测得的二氢嘧啶脱氢酶（DPD）活性是否与氟嘧啶治疗期间的不良事件相关。
进行了一项回顾性队列研究。研究人群包括481例接受氟嘧啶治疗的患者，这些患者的相关特征已知，且电子健康记录中记录了不良事件。使用对数回归校正了除DPD表型外可能影响不良事件发生率的因素。这些对数回归模型用于确定PBMCs中测得的DPD表型与不良事件之间的关联。
PBMCs中测得的DPD活性降低的患者发生更多不良事件。对数回归数据结果表明，在校正剂量、化疗方案和相关患者特征后，这种影响仍然显著。
发现PBMCs中DPD酶活性降低与不良事件之间存在显著相关性。本文的研究结果支持进一步探索DPD表型分析作为预防氟嘧啶相关不良事件的一种方法。DPD表型分析的进一步评估将需要在前瞻性研究中进行临床验证。
