Importance of and Strategies for Implementing DPYD Testing to Prevent Severe Fluoropyrimidine Chemotherapy Toxicity

DPYD (CPIC Level A variants: *2A, *13, c.2846A>T, HapB3)

DPYD variants → reduced dihydropyrimidine dehydrogenase (DPD) activity → fluoropyrimidine accumulation → dose-dependent toxicity; CPIC Level A: dose reduction recommended in DPD IM and PM

Practical reference article from ASCO Educational Book 2026 on implementing DPYD testing before fluoropyrimidines (5-FU, capecitabine). The authors detail testing strategies (genotyping vs DPD phenotyping), CPIC Level A variants to search for (*2A, *13, c.2846A>T, HapB3), dose reduction algorithms, and implementation challenges in healthcare systems. Severe fluoropyrimidine toxicity (grade 3-4) affects 10-40% of ungenotyped patients; DPYD-related deaths represent 0.5-1% of unscreened treatments.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

DPYD testing before fluoropyrimidines has been CPIC Level A since 2017 and recommended by EMA since 2020. Despite these recommendations, implementation remains heterogeneous in France. This ASCO 2026 article serves as the practical reference for oncologists and hospital pharmacists wishing to implement a systematic screening protocol.

CPIC Level A actionable +3; practical implementation recommendations +2; ASCO Ed Book (international reference) +2; death prevention +2