Pretreatment DPYD/DPD Testing: Clinical Updates and Considerations

Course overview

In this lecture, Dr. Yuan Ji focuses on pretreatment DPYD/DPD testing, one of the most extensively discussed or debated topics in clinical PGx implementation and oncology practice in recent years. Centered with real patient stories and the devastating fluoropyrimidines (FPs) toxicity-related mortality rate, Dr. Ji explains the basics of clinical pharmacology of FPs, in relation to the severe, sometimes life-threatening treatment-related toxicities in genetically predisposed dihydropyrimidine dehydrogenase (DPD) deficient patients and the importance of performing pretreatment DPYD/DPD testing in all FPs-treated patients. Additionally, Dr. Ji also reviews the history of the FDA's labeling updates for FPs, available dosing guidelines and resources for clinical implementation of DPYD genotype-guided dosing practice of FPs treatment and shares her insights of the Association for Molecular Pathology (AMP) PGx Working Group recommendation on DPYD genotyping alleles that aims to address the heterogeneity among clinical DPYD genotyping tests and to promote testing standardization across clinical laboratories. Lack of carefully designed and comprehensive DPYD testing with short turnaround time has been one of the several concerns of oncologists, impeding the clinical adoption of pretreatment DPYD/DPD testing for all cancer patients who hope to be cured rather than to be "killed" by the toxicities of their chemotherapy medications. After this presentation, participants will be able to: * Review fluoropyrimidines (FPs), dihydropyrimidine dehydrogenase (DPD), and DPD deficiency * Describe the association of DYPD variants with FPs-related toxicities * Clarify updates on professional guidelines and clinical practices * Review heterogeneity among clinical pharmacogenomic genotyping tests and introduce the AMP PGx Working Group recommendation on DPYD genotyping alleles * Discuss additional considerations of implementing clinical DPYD/DPD testing