Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience

Abstract

Background:Severe toxicity is experienced by a substantial minority of patients receiving fluoropyrimidine-based chemotherapy, with approximately 20% of these severe toxicities attributable to polymorphisms in the DPYD gene. The DPYD codes for the enzyme dihydropyrimidine dehydrogenase (DPD) important in the metabolism of fluoropyrimidine-based chemotherapy. We questioned whether prospective DPYD mutation analysis in all patients commencing such therapy would prove more cost-effective than reactive testing of patients experiencing severe toxicity.Methods:All patients experiencing severe toxicity from fluoropyrimidine-based chemotherapy for colorectal cancer in an Irish private hospital over a 3-year period were tested for 4 DPYD polymorphisms previously associated with toxicity. The costs associated with an index admission for toxicity in DPD-deficient patients were examined. A cost analysis was undertaken comparing the anticipated cost of implementing screening for DPYD mutations versus current usual care. One-way sensitivity analysis was conducted on known input variables. An alternative scenario analysis from the perspective of the Irish health-care payer (responsible for public hospitals) was also performed.Results:Of 134 patients commencing first-line fluoropyrimidine chemotherapy over 3 years, 30 (23%) patients developed grade 3/4 toxicity. Of these, 17% revealed heterozygote DPYD mutations. The cost of hospitalization for the DPYD-mutated patients was €232 061, while prospectively testing all 134 patients would have cost €23 718. Prospective testing would result in cost savings across all scenarios.Conclusions:The cost of hospital admission for severe chemotherapy-related toxicity is significantly higher than the cost of prospective DPYD testing of each patient commencing fluoropyrimidine chemotherapy.

Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

“…35 Accordingly, Murphy et al suggested that the cost resulting from the prolonged hospitalizations for severe fluoropyrimidine toxicity overweighs the cost of prospective DPYD testing of each patient initiating fluoropyrimidine chemotherapy. 36 Our case indicates that the upfront DPYD testing would have been not only lifesaving in terms of dosing optimization but also cost effective, comparing to the cost resulting from the 30 days of our patient's hospitalization.…”

Overcoming barriers to implementing precision dosing with 5‐fluorouracil and capecitabine

“…This work also highlights how establishing a multidisciplinary clinical working group can help to drive change in practice. Published cost analysis data showing upfront DPYD genotype‐guided dose individualisation results in cost saving or in worst case cost neutral outcomes could be used to support the implementation of testing in a healthcare setting 53,54 …”

Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper

“…Additional analyses demonstrated that the genotyping is cost-efficient [34, 36, 37]. In Switzerland both DPD testing of the 4 established DPYD variants and 5-FU therapeutic drug monitoring (TDM) are included as standard under the Swiss basic health insurance scheme.…”