Presentation: Patient requiring fluoropyrimidine-based chemotherapy
Genetic variants in the DPYD gene can cause deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which can leave affected individuals prone to severe and sometimes life-threatening adverse reactions to fluoropyrimidine-based chemotherapy.
Example clinical scenario
A 64-year-old man has been diagnosed with colon cancer and is due to start adjuvant chemotherapy containing 5-fluorouracil. Before starting his treatment, you plan to undertake testing for variants in the DPYD gene.
When to consider genomic testing
- All patients should have pharmacogenomic testing for partial or complete DPD deficiency before initiation of intravenous 5-fluorouracil, oral capecitabine or tegafur therapy.
What do you need to do?
- Consult the National Genomic Test Directory for cancer. From here, you can access information about individual tests and their associated eligibility criteria.
- For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
- For this indication, the appropriate test to choose is:
- M1.7 DPYD hotspot for the DPYD gene. This involves simple targeted DPYD variant testing. (Always check the latest test directory to ensure the test code is correct.)
- For DNA-based tests, an EDTA sample is required.
- Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
Resources
For clinicians
- Clinical Pharmacogenetics Implementation Consortium: Guideline for fluoropyrimidines and DPYD
- Medicines and Healthcare products Regulatory Agency: Drug safety update: 5-fluorouracil (intravenous), capecitabine, tegafur: DPD testing recommended before initiation to identify patients at increased risk of severe and fatal toxicity
- NHS England: Clinical commissioning urgent policy statement: Pharmacogenomic testing for DPYD polymorphisms with fluoropyrimidine therapies (PDF, 10 pages)
- UK Systemic Anti-Cancer Therapy Board: Personalised medicine approach for fluoropyrimidine-based therapies (PDF, eight pages)