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

Giuseppe Toffoli, Federico Innocenti, Jerry Polesel, Elena De Mattia, Franca Sartor, Chiara Dalle Fratte, Fabrizio Ecca, Eva Dreussi, Elisa Palazzari, Michela Guardascione, Angela Buonadonna, Luisa Foltran, Marica Garziera, Alessia Bignucolo, Stefania Nobili, Enrico Mini, Adolfo Favaretto, Massimiliano Berretta, Mario D'Andrea, Antonino De PaoliRossana Roncato, Erika Cecchin

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical Pharmacology and Therapeutics
DOIs
Publication statusAccepted/In press - Jan 1 2018

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Toffoli, G., Innocenti, F., Polesel, J., De Mattia, E., Sartor, F., Dalle Fratte, C., Ecca, F., Dreussi, E., Palazzari, E., Guardascione, M., Buonadonna, A., Foltran, L., Garziera, M., Bignucolo, A., Nobili, S., Mini, E., Favaretto, A., Berretta, M., D'Andrea, M., ... Cecchin, E. (Accepted/In press). The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice. Clinical Pharmacology and Therapeutics. https://doi.org/10.1002/cpt.1257