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

Autor: Alexander L T Imholz, Jesse J. Swen, Marlène H.W. van de Poel, Albert J. ten Tije, Paul Hamberg, Annemieke Cats, Femke M. de Man, Jos H. Beijnen, Miriam Koopman, Vincent O. Dezentjé, Emma Kienhuis, Caroline M.P.W. Mandigers, Peter Nieboer, Linda M. Henricks, Didier Meulendijks, André B.P. van Kuilenburg, Carin A.T.C. Lunenburg, Geert W.J. Frederix, Jan H.M. Schellens, Hilde Rosing, Henk-Jan Guchelaar, Helga J. Droogendijk, Rob L. H. Jansen, Frank J.F. Jeurissen, Ron H.J. Mathijssen, Hans Gelderblom, Arnold Baars, Geert Jan Creemers, Johanna E.A. Portielje, Erik van Werkhoven, Ron H.N. van Schaik
Přispěvatelé: APH - Methodology, APH - Personalized Medicine, Graduate School, CCA - Cancer Treatment and Quality of Life, Laboratory Genetic Metabolic Diseases, AGEM - Inborn errors of metabolism, Medical Oncology, Clinical Chemistry, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Medische Oncologie (9), Interne Geneeskunde, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
PREDICTOR
Cancer Research
FLUOROURACIL PLUS LEUCOVORIN
0302 clinical medicine
DPYD
Neoplasms
Genotype
Antineoplastic Combined Chemotherapy Protocols
Prospective Studies
ORAL CAPECITABINE
Precision Medicine
Prospective cohort study
health care economics and organizations
cost-analysis
pharmacogenetics
Prognosis
DEFICIENCY
030220 oncology & carcinogenesis
Cost analysis
Costs and Cost Analysis
5-FLUOROURACIL
Fluorouracil
Dihydropyrimidine dehydrogenase
medicine.drug
medicine.medical_specialty
Genotyping
fluoropyrimidines
Capecitabine
03 medical and health sciences
SDG 3 - Good Health and Well-being
Internal medicine
medicine
Journal Article
Humans
Cost-analysis
Genetic Testing
Dihydrouracil Dehydrogenase (NADP)
Polymorphism
Genetic
Toxicity
business.industry
dihydropyrimidine dehydrogenase
Fluoropyrimidines
toxicity
Clinical trial
METASTATIC COLORECTAL-CANCER
030104 developmental biology
genotyping
Pharmacogenetics
business
Zdroj: European Journal of Cancer, 107, 60. Elsevier Ltd
European Journal of Cancer, 107, 60. Elsevier Limited
European journal of cancer (Oxford, England, 107, 60-67. Elsevier Limited
European Journal of Cancer, 107, 60-67
European Journal of Cancer
European Journal of Cancer, 107, 60-67. Elsevier Ltd.
European Journal of Cancer, 107, 60-67. ELSEVIER SCI LTD
ISSN: 0959-8049
Popis: 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 (sic)2599 per patient compared with (sic)2650 for non-screening, resulting in a net cost saving of (sic)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. (C) 2018 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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