Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
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Data availability
The dataset generated and analysed during the current study is available from the corresponding author on reasonable request.
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Conceptualization: A. D. and P. L.; methodology: A. D., P. L., and A. W.; formal analysis and investigation: K. D., P. L. and A. D.; writing original draft preparation: K. D.; manuscript review and editing: K. D., P. L., G. B., A. W. and A. D.; supervision: A. D.
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This research study was conducted retrospectively from the data obtained for clinical purposes. We consulted extensively with the local scientific committee of Tergooi Medical Center which determined that our study did not need ethical approval.
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Doornhof, K.R., van der Linden, P.D., Boeke, G.M. et al. Dihydropyrimidine dehydrogenase phenotype in peripheral blood mononuclear cells is related to adverse events of fluoropyrimidine-therapy. Eur J Clin Pharmacol 79, 493–501 (2023). https://doi.org/10.1007/s00228-023-03466-8
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DOI: https://doi.org/10.1007/s00228-023-03466-8