Linda M Henricks1, Carin A T C Lunenburg2, Femke M de Man3, Didier Meulendijks4, Geert W J Frederix5, Emma Kienhuis3, Geert-Jan Creemers6, Arnold Baars7, Vincent O Dezentjé8, Alexander L T Imholz9, Frank J F Jeurissen10, Johanna E A Portielje11, Rob L H Jansen12, Paul Hamberg13, Albert J Ten Tije14, Helga J Droogendijk15, Miriam Koopman16, Peter Nieboer17, Marlène H W van de Poel18, Caroline M P W Mandigers19, Hilde Rosing20, Jos H Beijnen21, Erik van Werkhoven22, André B P van Kuilenburg23, Ron H N van Schaik24, Ron H J Mathijssen3, Jesse J Swen25, Hans Gelderblom2, Annemieke Cats26, Henk-Jan Guchelaar25, Jan H M Schellens27. 1. 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. 2. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands. 4. 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. 5. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 6. Department of Medical Oncology, Catharina Hospital, Eindhoven, the Netherlands. 7. Department of Internal Medicine, Hospital Gelderse Vallei, Ede, the Netherlands. 8. Department of Internal Medicine, Reinier de Graaf Hospital, Delft, the Netherlands; Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 9. Department of Internal Medicine, Deventer Hospital, Deventer, the Netherlands. 10. Department of Internal Medicine, Haaglanden Medical Center, The Hague, the Netherlands. 11. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Haga Hospital, The Hague, the Netherlands. 12. Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands. 13. Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Rotterdam, the Netherlands. 14. Department of Internal Medicine, Amphia Hospital, Breda, the Netherlands. 15. Department of Internal Medicine, Bravis Hospital, Roosendaal, the Netherlands. 16. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 17. Department of Internal Medicine, Wilhelmina Hospital Assen, Assen, the Netherlands. 18. Department of Internal Medicine, Laurentius Hospital, Roermond, the Netherlands. 19. Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 20. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 21. 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. 22. Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 23. Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam Gastroenterology & Metabolism, Amsterdam, the Netherlands. 24. Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, the Netherlands. 25. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands. 26. Department of Gastrointestinal Oncology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands. 27. 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.
Abstract
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.
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.
Authors: Apostolos Tsiachristas; Grant Vallance; Rositsa Koleva-Kolarova; Harriet Taylor; Luke Solomons; Giovanni Rizzo; Catherine Chaytor; Junel Miah; Sarah Wordsworth; A Bassim Hassan Journal: BMC Cancer Date: 2022-04-26 Impact factor: 4.638