• Linda M Henricks, Carin A T C Lunenburg, Femke M de Man, Didier Meulendijks, Geert W J Frederix, Emma Kienhuis, Geert-Jan Creemers, Arnold Baars, Vincent O Dezentjé, Alexander L T Imholz, Frank J F Jeurissen, Johanna E A Portielje, JansenRob L HRLHDepartment of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands., Paul Hamberg, Albert J Ten Tije, Helga J Droogendijk, Miriam Koopman, Peter Nieboer, Marlène H W van de Poel, Caroline M P W Mandigers, Hilde Rosing, Jos H Beijnen, Erik van Werkhoven, van KuilenburgAndré B PABPLaboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, the Netherlands., van SchaikRon H NRHNDepartment of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands., MathijssenRon H JRHJDepartment of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands., Jesse J Swen, Hans Gelderblom, Annemieke Cats, Henk-Jan Guchelaar, and SchellensJan H MJHMDivision of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Division of Pharmac.
• Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. Electronic address: l.henricks@nki.nl.
• Eur. J. Cancer. 2019 Jan 1; 107: 60-67.

BackgroundFluoropyrimidine therapy including capecitabine or 5-fluorouracil can result in severe treatment-related toxicity in up to 30% of patients. Toxicity is often related to reduced activity of dihydropyrimidine dehydrogenase, the main metabolic fluoropyrimidine enzyme, primarily caused by genetic DPYD polymorphisms. In a large prospective study, it was concluded that upfront DPYD-guided dose individualisation is able to improve safety of fluoropyrimidine-based therapy. In our current analysis, we evaluated whether this strategy is cost saving.MethodsA cost-minimisation analysis from a health-care payer perspective was performed as part of the prospective clinical trial (NCT02324452) in which patients prior to start of fluoropyrimidine-based therapy were screened for the DPYD variants DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A and received an initial dose reduction of 25% (c.2846A>T, c.1236G>A) or 50% (DPYD*2A, c.1679T>G). Data on treatment, toxicity, hospitalisation and other toxicity-related interventions were collected. The model compared prospective screening for these DPYD variants with no DPYD screening. One-way and probabilistic sensitivity analyses were also performed.ResultsExpected total costs of the screening strategy were €2599 per patient compared with €2650 for non-screening, resulting in a net cost saving of €51 per patient. Results of the probabilistic sensitivity and one-way sensitivity analysis demonstrated that the screening strategy was very likely to be cost saving or worst case cost-neutral.ConclusionsUpfront DPYD-guided dose individualisation, improving patient safety, is cost saving or cost-neutral but is not expected to yield additional costs. These results endorse implementing DPYD screening before start of fluoropyrimidine treatment as standard of care.Copyright © 2018 Elsevier Ltd. All rights reserved.

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