Basic & clinical pharmacology & toxicology · 2022
DPYD genotyping and dihydropyrimidine dehydrogenase (DPD) phenotyping in clinical oncology. A clinically focused minireview.
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Paulsen Niels Herluf, Vojdeman Fie, Andersen Stig Ejdrup, Bergmann Troels K, Ewertz Marianne, Plomgaard Peter, Hansen Morten Rix, Esbech Peter Skov, Pfeiffer Per, Qvortrup Camilla, Damkier Per
Аннотация
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.
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.