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The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice.
Toffoli, Giuseppe; Innocenti, Federico; Polesel, Jerry; De Mattia, Elena; Sartor, Franca; Dalle Fratte, Chiara; Ecca, Fabrizio; Dreussi, Eva; Palazzari, Elisa; Guardascione, Michela; Buonadonna, Angela; Foltran, Luisa; Garziera, Marica; Bignucolo, Alessia; Nobili, Stefania; Mini, Enrico; Favaretto, Adolfo; Berretta, Massimiliano; D'Andrea, Mario; De Paoli, Antonino; Roncato, Rossana; Cecchin, Erika.
Afiliação
  • Toffoli G; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Innocenti F; Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Polesel J; Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, PN, Italy.
  • De Mattia E; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Sartor F; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Dalle Fratte C; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Ecca F; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Dreussi E; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Palazzari E; Radiation Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Guardascione M; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Buonadonna A; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Foltran L; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Garziera M; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Bignucolo A; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Nobili S; Department of Health Sciences, University of Florence, Firenze, Italy.
  • Mini E; Department of Health Sciences, University of Florence, Firenze, Italy.
  • Favaretto A; Medical Oncology Unit, Ospedale Cà Foncello, Treviso, Italy.
  • Berretta M; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • D'Andrea M; Medical Oncology Unit, "San Filippo Neri Hospital,", Rome, Italy.
  • De Paoli A; Radiation Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Roncato R; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
  • Cecchin E; Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081, Aviano, Italy.
Clin Pharmacol Ther ; 105(4): 994-1002, 2019 04.
Article em En | MEDLINE | ID: mdl-30339275
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Neoplasias Colorretais / Di-Hidrouracila Desidrogenase (NADP) / Antineoplásicos Tipo de estudo: Etiology_studies / Health_economic_evaluation / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Neoplasias Colorretais / Di-Hidrouracila Desidrogenase (NADP) / Antineoplásicos Tipo de estudo: Etiology_studies / Health_economic_evaluation / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article