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.

Additional Metadata
Keywords Cost-analysis, Dihydropyrimidine dehydrogenase, DPYD, Fluoropyrimidines, Genotyping, Pharmacogenetics, Toxicity
Persistent URL dx.doi.org/10.1016/j.ejca.2018.11.010, hdl.handle.net/1765/113094
Journal European Journal of Cancer
Citation
Henricks, L.M. (Linda M.), Lunenburg, C.A.T.C. (Carin A.T.C.), de Man, F.M, Meulendijks, D, Frederix, G.W.J, Kienhuis, E, … Schellens, J.H.M. (Jan H.M.). (2019). A cost analysis of upfront DPYD genotype–guided dose individualisation in fluoropyrimidine-based anticancer therapy. European Journal of Cancer, 107, 60–67. doi:10.1016/j.ejca.2018.11.010