title: Evaluation of clinical implementation of prospective DPYD genotyping in 5-fluorouracil- or capecitabine-treated patients.
abstract: Fluoropyrimidines are commonly used anti-cancer drugs, but lead to severe toxicity in 10-30% of patients. Prospective DPYD screening identifies patients at risk for toxicity and leads to a safer treatment with fluoropyrimidines. This study evaluated the routinely application of prospective DPYD screening at the Leiden University Medical Center.
  
  
  
  Prospective DPYD screening as part of routine patient care was evaluated by retrospectively screening databases and patient files to determine genotype, treatment, dose recommendations and dose adjustments.
  
  
  
  86.9% of all patients with a first fluoropyrimidine prescription were screened. Fourteen out of 275 patients (5.1%) carried a DPYD variant and received a 25-50% dose reduction recommendation. None of the patients with a DPYD variant treated with a reduced dose developed toxicities.
  
  
  
  Prospective DPYD screening can be implemented successfully in a real world clinical setting, is well accepted by physicians and results in low toxicity.
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Carin Atc
authors.initials: CA
authors.lastname: Lunenburg
authors.affiliation: Department of Pharmacy, Treant Healthgroup, The Netherlands.|Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maurice C
authors.initials: MC
authors.lastname: van Staveren
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Swen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005838:Genotype; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D000069287:Capecitabine; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil
keywords: 5-fluorouracil; DPYD; capecitabine; dihydropyrimidine dehydrogenase; dose reductions; fluoropyrimidines; implementation; screening