Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Medical Oncology, Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Br J Clin Pharmacol. 2024 Jan;90(1):336-343. doi: 10.1111/bcp.15918. Epub 2023 Oct 13.
With the rising number of oral targeted oncolytics and growing awareness of the benefits of therapeutic drug monitoring (TDM) within the field of oncology, it is expected that the requests for quantifying concentrations of these drugs will increase. It is important to (cross-)validate available assays and ensure its quality, as results may lead to altered dosing recommendations. Therefore, we aimed to evaluate the performance of laboratories measuring concentrations of targeted oral oncolytics in a one-time international quality control (QC) programme.
Participating laboratories received a set of plasma samples containing low, medium and high concentrations of imatinib, sunitinib, desethylsunitinib, pazopanib, cabozantinib, olaparib, enzalutamide, desmethylenzalutamide and abiraterone, with the request to report their results back within five weeks after shipment. Accuracy was defined acceptable if measurements where within 85%-115% from the weighed-in reference concentrations. Besides descriptive statistics, an exploratory ANOVA was performed.
Seventeen laboratories from six countries reported 243 results. Overall, 80.7% of all measurements were within the predefined range of acceptable accuracy. Laboratories performed best in quantifying imatinib and poorest in quantifying desethylsunitinib (median absolute inaccuracy respectively 4.0% (interquartile range (IQR) 1.8%-6.5%) and 15.5% (IQR 8.8%-34.9%)). The poorest performance of desethylsunitinib might be caused by using the stable-isotope-labelled sunitinib instead of desethylsunitinib as an internal standard, or due to the light-induced cis(Z)/trans(E) isomerization of (desethyl)sunitinib. Overall, drug substance and performing laboratory seemed to influence the absolute inaccuracy (F = 16.4; p < 0.001 and F = 35.5; p < 0.001, respectively).
Considering this is the first evaluation of an international QC programme for oral targeted oncolytics, an impressive high percentage of measurements were within the predefined range of accuracy. Cross-validation of assays that are used for dose optimization of oncolytics will secure the performance and will protect patients from incorrect advices.
随着口腔靶向肿瘤药物的数量不断增加，以及肿瘤领域对治疗药物监测（TDM）益处的认识不断提高，预计对这些药物浓度进行定量的需求将会增加。因此，验证现有的检测方法并确保其质量非常重要，因为检测结果可能会导致剂量调整建议的改变。因此，我们旨在通过一次性国际质量控制（QC）计划评估测量口腔靶向肿瘤药物浓度的实验室的性能。
参与实验室收到了一套包含低、中、高浓度伊马替尼、舒尼替尼、去乙基舒尼替尼、帕唑帕尼、卡博替尼、奥拉帕利、恩杂鲁胺、去甲基恩杂鲁胺和阿比特龙的血浆样本，并要求在收到样本后五周内报告结果。如果测量值在称重参考浓度的 85%-115%范围内，则定义为准确度可接受。除了描述性统计外，还进行了探索性方差分析。
来自六个国家的 17 个实验室报告了 243 个结果。总体而言，80.7%的测量值在可接受的准确度范围内。实验室在定量测定伊马替尼方面表现最好，在定量测定去乙基舒尼替尼方面表现最差（中位数绝对误差分别为 4.0%（四分位距（IQR）1.8%-6.5%）和 15.5%（IQR 8.8%-34.9%））。去乙基舒尼替尼表现不佳可能是由于使用稳定同位素标记的舒尼替尼而不是去乙基舒尼替尼作为内标，或者由于（去乙基）舒尼替尼的光诱导顺式（Z）/反式（E）异构化。总体而言，药物物质和执行实验室似乎影响绝对误差（F=16.4；p<0.001 和 F=35.5；p<0.001）。
考虑到这是口腔靶向肿瘤药物国际 QC 计划的首次评估，令人印象深刻的是，大量测量值在可接受的准确度范围内。对用于优化肿瘤药物剂量的检测方法进行交叉验证将确保其性能，并保护患者免受错误建议的影响。
