Abstract
Background: In clinical oncology, systemic 5-fluorouracil (5-FU) and its oral pro-drugs are used to treat a broad group of solid tumours. Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency are at elevated risk of toxicity if treated with standard doses of 5-FU. DPYD genotyping and measurements of plasma uracil concentration (DPD phenotyping) can be applied as tests for DPD deficiency. In April 2020, the European Medicines Agency recommended pre-treatment DPD testing to reduce the risk of 5-FU-related toxicity. Objectives: The objective of this study is to present the current evidence for DPD testing in routine oncological practice. Methods: Two systematic literature searches were performed following the PRISMA guidelines. We identified studies examining the possible benefit of DPYD genotyping or DPD phenotyping on the toxicity risk. Findings: Nine and 12 studies met the criteria for using DPYD genotyping and DPD phenotyping, respectively. Conclusions: The evidence supporting either DPYD genotyping or DPD phenotyping as pre-treatment tests to reduce 5-FU toxicity is poor. Further evidence is still needed to fully understand and guide clinicians to dose by DPD activity.
Original language | English |
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Journal | Basic and Clinical Pharmacology and Toxicology |
Volume | 131 |
Issue number | 5 |
Pages (from-to) | 325-346 |
Number of pages | 22 |
ISSN | 1742-7835 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
Keywords
- acute
- cancer chemotherapy
- gene expression/regulation
- pharmacokinetics
- safety evaluation
- SNPs
- toxicity