Test DPYD, UGT1A1 and TPMT/NUDT15 before the first dose, everywhere

Overview

• Protocol upgrade, graded proven but unevenly used, on the DPYD evidence. In 17 Dutch hospitals, 85 of 1,103 evaluable patients (8 per cent) carried one of four DPYD variants; with genotype-guided dose reduction the relative risk of severe toxicity in DPYD*2A carriers was 1.31, against 2.87 in a historical cohort given full doses (Henricks, 2018). A 2022 meta-analysis of 17 studies found pharmacogenetics-guided dosing reduced grade 3 or 4 toxicity (risk ratio 0.32, 95 per cent confidence interval 0.27 to 0.39) with no difference in response (Glewis, 2022).
• Adoption gap, as measured: in a 2021 survey after NHS England commissioned the test, 131 of 138 United Kingdom organisations (94.9 per cent) reported testing all patients receiving fluoropyrimidines, with turnaround from under 2 days to more than 10 (Shaunak, 2025). Across 28 sites in 9 countries in the Pharmacogenomics Global Research Network, only 2 reported testing more than 75 per cent of patients due a fluoropyrimidine, 70 per cent relied on clinicians remembering to order the test, and median turnaround was 10 days (El Rouby, 2026).