A cost analysis of upfront DPYD genotype-guided dose individualisation in fluoropyrimidine-based anticancer therapy.

Autor: Henricks LM; 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., Lunenburg CATC; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands., de Man FM; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands., Meulendijks D; 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; Dutch Medicines Evaluation Board (CBG-MEB), Utrecht, the Netherlands., Frederix GWJ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands., Kienhuis E; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands., Creemers GJ; Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands., Baars A; Department of Internal Medicine, Hospital Gelderse Vallei, Ede, the Netherlands., Dezentjé VO; Department of Internal Medicine, Reinier de Graaf Hospital, Delft, the Netherlands; Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Imholz ALT; Department of Internal Medicine, Deventer Hospital, Deventer, the Netherlands., Jeurissen FJF; Department of Internal Medicine, Haaglanden Medical Center, The Hague, the Netherlands., Portielje JEA; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands., Jansen RLH; Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands., Hamberg P; Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, the Netherlands., Ten Tije AJ; Department of Internal Medicine, Amphia Hospital, Breda, the Netherlands., Droogendijk HJ; Department of Internal Medicine, Bravis Hospital, Roosendaal, the Netherlands., Koopman M; Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Nieboer P; Department of Internal Medicine, Wilhelmina Hospital Assen, Assen, the Netherlands., van de Poel MHW; Department of Internal Medicine, Laurentius Hospital, Roermond, the Netherlands., Mandigers CMPW; Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands., Rosing H; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Beijnen JH; Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands., van Werkhoven E; Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands., van Kuilenburg ABP; Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, the Netherlands., van Schaik RHN; Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands., Swen JJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands., Gelderblom H; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands., Cats A; Department of Gastrointestinal Oncology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Guchelaar HJ; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands., Schellens JHM; 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; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2019 Jan; Vol. 107, pp. 60-67. Date of Electronic Publication: 2018 Dec 11.
DOI: 10.1016/j.ejca.2018.11.010
Abstrakt: Background: Fluoropyrimidine 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.
Methods: A 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.
Results: Expected 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.
Conclusions: Upfront 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.)
Databáze: MEDLINE
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