Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy.

To evaluate toxicity risk in carriers of four variants using an institutional genetic repository. Of over 65,000 patients in the repository, 582 were evaluated for the primary composite end point of grade 3 or higher toxicity or treatment modification due to toxicity. The primary end point was more common in variant carriers (36.5 vs 18.1%, adjusted odds ratio 2.42, 95% CI: 1.05-5.55, p = 0.04), and in patients with decreased DPD activity (≤1 vs 2) (75.6 vs 17.0%, adjusted odds ratio 16.31, 95% CI: 2.64-100.68, p = 0.003). Patients carrying any of the four variants are at increased risk of severe toxicity or subsequent treatment modifications, suggesting such patients may benefit from genotype-informed treatment.