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Implementation of pharmacogenomic DPYD-guided fluoropyrimidine dosing for cancer patients in Saskatchewan, Canada

Laboratory Genetics and Genomics
  • Primary Categories:
    • Laboratory Genetics
  • Secondary Categories:
    • Laboratory Genetics
Introduction:
Dihydropyrimidine dyhdrogenase (DPD) is the key enzyme responsible for the metabolism and inactivation of fluoropyrimidine drugs, like 5-fluorouracil (5-FU) and capecitabine, used in chemotherapy treatment. Patients with reduced DPD enzyme activity are at high risk of severe side effects from standard doses of these drugs when receiving chemotherapy treatment. Genetic variants in DPYD, the gene encoding DPD enzyme, have been associated with reduced enzyme activity. A joint consensus from Oncologists across Canada recommend DPYD testing before chemotherapy. Previously, testing were referred to a laboratory outside of Saskatchewan after patients reported experiencing symptoms, with results taking approximately two to three weeks. Therefore, there is an urgent need to implement a local such testing to prevent drug toxicity and improve patient safety. 

Methods:
DPYD genotyping is performed at RUH Genomics Laboratory for cancer patients prior to receiving chemotherapy treatment, to rapidly detect six of the most common genetic variants that are known to indicate DPD deficiency, with results available in two to seven days. This test was first piloted in Saskatoon in May 2024. In July 2024, testing was expanded and made available to cancer patients across the province. This ensures thorough detection of over 95% of DPD deficiencies within the population. In addition, validation of an in house DPYD full gene sequencing is in progress to detect rare variants other than the most common ones. 

 

Results:
So far, 202 cancer patients have been subjected to DPYD genotyping prior to chemotherapy. 13 of them were detected to have a reduced function or non-function allele, which accounts for ~ 6.5% in patient population. Their doses of 5-FU/capecitabine were adjusted accordingly to prevent the risk of severe side effects. 

Conclusion:
DPYD testing allows for the early detection of DPD deficiencies, which improves patient outcomes by adjusting the dosage of fluoropyrimidine drugs used in chemotherapy treatment, overall reducing the risk of severe side effects. Local availability of these tests allows cancer patients to access safe, effective treatment much faster. 

 

Agenda

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