TY - JOUR
T1 - The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice
AU - Toffoli, Giuseppe
AU - Innocenti, Federico
AU - Polesel, Jerry
AU - De Mattia, Elena
AU - Sartor, Franca
AU - Dalle Fratte, Chiara
AU - Ecca, Fabrizio
AU - Dreussi, Eva
AU - Palazzari, Elisa
AU - Guardascione, Michela
AU - Buonadonna, Angela
AU - Foltran, Luisa
AU - Garziera, Marica
AU - Bignucolo, Alessia
AU - Nobili, Stefania
AU - Mini, Enrico
AU - Favaretto, Adolfo
AU - Berretta, Massimiliano
AU - D'Andrea, Mario
AU - De Paoli, Antonino
AU - Roncato, Rossana
AU - Cecchin, Erika
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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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U2 - 10.1002/cpt.1257
DO - 10.1002/cpt.1257
M3 - Article
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
ER -