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Published on: February 6, 2015
Results of the first international quality control programme for oral targeted oncolytics
Eline L Giraud1, Lindsey M H Te Brake1, Erik C A van den Hombergh1
1Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Aims:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
Insights
This quality control program found 80.7% of lab measurements for oral targeted oncolytics were accurate. This ensures reliable therapeutic drug monitoring (TDM) for better cancer treatment dosing.
Area of Science:
- Oncology
- Analytical Chemistry
- Clinical Pharmacology
Background:
- The increasing use of oral targeted oncolytics necessitates reliable therapeutic drug monitoring (TDM).
- Assay validation is crucial for accurate drug concentration measurements, impacting dosing decisions in cancer therapy.
Purpose of the Study:
- To evaluate the performance of laboratories in quantifying oral targeted oncolytic concentrations.
- To assess the quality of measurements in an international quality control (QC) program for these drugs.
Main Methods:
- Seventeen laboratories from six countries participated in a one-time international QC program.
- Plasma samples with varying concentrations of nine oral targeted oncolytics were analyzed.
- Accuracy was defined as measurements within 85%-115% of reference concentrations; ANOVA was used for analysis.
Main Results:
- Overall, 80.7% of 243 reported measurements met the accuracy criteria.
- Laboratory performance varied, with highest accuracy for imatinib and poorest for desethylsunitinib.
- Factors such as drug substance and laboratory influenced measurement inaccuracy.
Conclusions:
- The study demonstrates a high percentage of accurate measurements in the first international QC program for oral targeted oncolytics.
- Cross-validation of assays is essential for reliable dose optimization and patient safety.
- Ensuring assay performance protects patients from potentially incorrect treatment advice.
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