Should DPD analysis be required prior to prescribing fluoropyrimidines?

Area of Science:

• Biochemistry
• Pharmacogenomics
• Oncology

Background:

• Dihydropyrimidine dehydrogenase (DPD) is essential for metabolizing 5-fluorouracil (5FU) and capecitabine chemotherapy.
• Genetic variations in the DPYD gene can lead to reduced DPD enzyme activity.
• DPD deficiency is linked to severe toxicities in patients receiving 5FU-based therapies.

Purpose of the Study:

• To review the performance of current assays for assessing DPD enzyme activity and DPYD gene status.
• To evaluate the clinical robustness of these assays for routine use.
• To identify needs for future improvements in DPD testing.

Main Methods:

• Literature review of assays assessing DPD enzyme activity.
• Analysis of DPYD genetic variants and their functional impact.
• Evaluation of assay performance for clinical application.

Main Results:

• Several DPYD gene variants impact DPD enzymatic activity.
• Current DPD and DPYD testing strategies are not adequate for routine clinical implementation.
• No current assay is robust enough to mandate routine DPD testing before fluoropyrimidine therapy.

Conclusions:

• Prospective identification of patients at risk for DPD deficiency is needed.
• Technological advancements are required to improve DPD testing.
• Improved testing could reduce severe side effects from 5FU chemotherapy.