Presentation: Patient requiring fluoropyrimidine-based chemotherapy

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.

• All patients should have pharmacogenomic testing for partial or complete DPD deficiency before initiation of intravenous 5-fluorouracil, oral capecitabine or tegafur therapy.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
• • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information about the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• 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.)
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications were 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.

For clinicians

• Clinical Pharmacogenetics Implementation Consortium (CPIC): 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)

For patients