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. 2019 Apr;105(4):994-1002.
doi: 10.1002/cpt.1257. Epub 2018 Nov 22.

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

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

Giuseppe Toffoli et al. Clin Pharmacol Ther. .

Abstract

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 (€2,972; 95% confidence interval (CI), €2,456-€3,505) than noncarriers (€825; 95% CI, €785-€864) (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 €2,975. 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.

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