The genotype for DPYD risk variants in colorectal cancer patients and the related toxicity management costs in clinical practice.

Toffoli G1, Innocenti F2, Polesel J3, De Mattia E1, Sartor F1, Fratte CD1, Ecca F1, Dreussi E1, Palazzari E4, Guardascione M1, Buonadonna A5, Foltran L5, Garziera M1, Bignucolo A1, Nobili S6, Mini E6, Favaretto A7, Berretta M5, D'Andrea M8, De Paoli A4, Roncato R1, Cecchin E1.

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Abstract

Lack of information on the clinical utility of preemptive DPYD screening prior to fluoropyrimidine treatment is a major barrier preventing its utilization 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 colorectal cancer patients 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%CI 2,456-3,505) than noncarriers (825€, 95%CI 785-864) (P<0.0001) and had a higher risk for toxicity requiring hospitalization (OR=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. This article is protected by copyright. All rights reserved.