Canada’s Drug Agency Publishes New Report on Enzyme Deficiency Testing for Patients Receiving Fluoropyrimidine-Based Chemotherapy

Canada’s Drug Agency has conducted a new health technology review exploring the evolving landscape of dihydropyrimidine dehydrogenase (DPD) enzyme deficiency testing for patients in Canada receiving a fluoropyrimidine-based chemotherapy — such as 5-fluorouracil or capecitabine. The review underscores that while DPD deficiency testing is now available in certain regions in Canada, access remains uneven across provinces and territories, prompting concerns about equity in patient care.
Between January 1, 2019, and February 5, 2025, Health Canada received 10 reports of severe toxicity linked to systemic fluoropyrimidine-based chemotherapy in patients in Canada with DPD deficiency. Of these 10 patients, 6 cases resulted in death. From this, key messages for health care professionals include increasing awareness of DPD deficiency, considering testing for patients receiving fluoropyrimidine treatment, and recognizing the limitations of current testing methods.

What Is the Issue?

Fluoropyrimidines are commonly used to treat solid tumor cancers, but patients with a deficiency in DPD (the enzyme needed to break down these drugs) are at high risk of severe toxicity and even death. Internationally, pretreatment DPD deficiency testing via genotyping or phenotyping is recommended to reduce adverse drug reactions through appropriate dose adjustments. However, the evidence supporting this approach is largely based on genetic variants identified in populations from European countries. This reliance on European data raises questions regarding the safety and effectiveness of these measures when applied to the ethnically diverse patient population in Canada, which is further compounded by inconsistent access to DPD deficiency testing in the country.

What Did We Do?

A survey was conducted to assesses the current state of DPD deficiency testing across Canada. In parallel, we executed a rapid review to identify and summarize evidence comparing the clinical effectiveness and cost-effectiveness of DPD deficiency testing and test-guided dose adjustments versus usual care. Our research methods included searches of major journal citation databases and a focused internet search using predefined criteria for relevant evidence published since 2015.

What Did We Find?

Our survey results indicated that, at the time of survey completion, DPYD genotyping is performed in 5 Canadian provinces, with 1 province also offering DPD phenotyping as needed, and testing costs range from CA$50 to CA$500 depending on the testing platform and required turnaround time. Additionally, the results also indicated that data supporting genotype-guided dosing primarily come from European study populations, confirming the limitations of their applicability to the multiethnic context in Canada. Further research and guideline development are needed to validate and establish the utility of genetic variants more common in populations outside of Europe. 

What Does This Mean?

Based on the evidence compiled in this review, DPYD genotyping may be a clinically valid and cost-effective strategy to improve the safety of fluoropyrimidine chemotherapy for people in Canada who are of European descent. However, given the lack of robust data for other ethnic groups, the broader applicability of this testing remains uncertain. Clinicians and decision-makers are encouraged to use the findings presented here to inform discussions around the implementation of DPD deficiency testing across Canada, with an eye toward both patient safety and health equity.