Dihydropyrimidine Dehydrogenase (DPD) Biomarker
What is the DPD biomarker?
The DPYD gene is present in each of the cells in our body. The gene holds the instructions for making a protein called dihydropyrimidine dehydrogenase (DPD). The normal (wild type) dihydropyrimidine dehydrogenase protein is an enzyme that breaks down fluorouracil-based chemotherapy drugs commonly used in colorectal cancer treatment and converts them from toxic to non-toxic molecules so they can be removed from the body.
Patients with a DPYD gene mutation either have: 1) a less efficient enzyme, or 2) complete loss of the enzyme. Therefore, those patients cannot metabolize drugs such as 5-Fluorouracil (5FU) and similar fluoropyrimidine-based chemotherapies (FOLFOX, FOLFIRI, FOLFIRINOX, capecitabine, and TAS-102). Patients with less-efficient enzyme activity (intermediate metabolizers) who are treated with 5FU or similar drugs may experience severe side effects like neutropenia (low white blood cells increasing the risk of infections), diarrhea, and mucositis (inflammation and ulceration from mouth to anus). Patients with no enzyme activity at all may experience
What does a DPYD mutation mean?
Experts know that there are more than 50 different mutations in the DPYD gene. About 5-18% of colorectal cancer patients have mutations in the DPYD gene but only about 1 in 1000 patients have no activity at all.
When and how should I have DPD biomarker testing?
Testing for DPD mutations is not required. Patients usually get tested after experiencing severe toxicity during treatment with fluoropyrimidine-based chemotherapy (5-FU or similar drugs such as FOLFOX, FOLFIRI, FOLFIRINOX, Capecitabine including TAS-102). Toxicity warnings are included on the FDA-approved labels of fluoropyrimidine-based chemotherapy agents.
What do I do with this information?
Every treatment has the potential to cause some side effects. Some people may be more sensitive than others to a drug. If you are experiencing severe side effects during treatment with fluoropyrimidine-based chemotherapy (5-FU or similar drugs such as FOLFOX, FOLFIRI, FOLFIRINOX, Capecitabine, or TAS-102), call your doctor immediately. You should also discuss pharmacogenomic testing (which identifies how your genes affect your response to drugs) with your doctor. It may show if you have a mutation in the DPYD gene that puts you at risk for severe toxicity or side effects.
The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends lower doses of chemotherapy based on the type of DPYD gene mutations or the level of activity. For patients with complete loss of enzyme activity, fluoropyrimidine-based chemotherapy should be stopped immediately. You should discuss other chemotherapy treatment options with your doctor.
For more on side effects of other chemotherapy regimens, click here.
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