The Genotype for DPYD Risk Variants in Patients with Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice

Lack of information on the clinical utility of preemptive DPYD screening before fluoropyrimidine treatment is a major barrier preventing its use in clinical practice. This study aimed to define the association between DPYD variants and fluoropyrimidine-related toxicity management costs. A cost analysis was conducted on the toxicities experienced by 550 patients with colorectal cancer treated with fluoropyrimidine-based chemotherapy. Genotyping for DPYD*2A, DPYD*13, DPYDc. 2846A>T, DPYD-HapB3, and UGT1A1*28 was done retrospectively and did not affect patients' treatments. Carriers of at least one DPYD variant experienced higher toxicity management costs (euro2,972; 95% confidence interval (CI), euro2,456-euro3,505) than noncarriers (euro825; 95% CI, euro785-euro864) (P < 0.0001) and had a higher risk for toxicity requiring hospitalization (odds ratio, 4.14; 95% CI, 1.87-9.14). In patients receiving fluoropyrimidine/irinotecan, the incremental cost between DPYD variant and UGT1A1*28/*28 carriers and noncarriers was euro2,975. This study suggests that the toxicity management costs during fluoropyrimidine-based therapy are associated with DPYD and UGT1A1*28 variants and supports the utility of genotyping.