FDA and NCCN Updates to DPYD-Guided 5-FU and Capecitabine Dosing for Oncologists

This presentation provides a practical update for medical oncologists on the 2025 FDA capecitabine boxed-warning change and the NCCN v5.2025 recommendation for pretreatment DPYD testing. It will focus on identifying patients at highest risk for toxicity, selecting a trustworthy DPYD test, translating genotype results into CPIC-guided dosing recommendations for 5-FU and capecitabine, and recognizing and managing severe toxicity.

Lecture Presenter
Ryan Nelson, PharmD
Ryan Nelson, PharmD
Adjunct Professor, Spencer Fox Eccles School of Medicine at the University of Utah
Medical Director, Precision Medicine, ARUP Laboratories

Ryan Nelson is a medical director of precision medicine at ARUP Laboratories and an adjunct professor at the Spencer Fox Eccles School of Medicine at the University of Utah. He received his doctorate degree in pharmacy from the University of Utah College of Pharmacy. He then completed a fellowship in personalized cancer medicine at Moffitt Cancer Center. He is a member of the American Society of Health-System Pharmacists, the American Society of Hematology, and the Clinical Pharmacogenetics Implementation Consortium. Dr. Nelson specializes in applied precision medicine with an emphasis on somatic and germline pharmacogenomics as well as pharmacoeconomics. His research interests include clinical utility and value of pharmacogenomics, gene-drug pair assessment for future implementation, and patient adherence to pharmacotherapy.

Objectives

After this presentation, participants will be able to:

Interpret the 2025 FDA (capecitabine boxed warning) and NCCN (v5.2025) updates on pretreatment DPYD testing for 5-FU and capecitabine, including their stated limitations, and identify patients at highest risk for severe or fatal DPD-deficiency toxicity
Assess whether a DPYD test covers the clinically important variants (CPIC/AMP Tier 1, including HapB3) and meets the laboratory quality and reporting standards needed to trust and act on its results.
Apply the CPIC guideline to convert a DPYD genotype into an activity score, predicted phenotype, and starting dose recommendation for 5-FU and capecitabine, then use early monitoring and dose titration to preserve efficacy while avoiding toxicity
Operationalize DPYD testing in the clinic, including urgent treatment scenarios, manage early-onset severe toxicity regardless of genotype result, when to suspect DPD deficiency, and how to use uridine triacetate within its 96-hour window