DPYD Genotyping to Guide Fluoropyrimidine Dosing

The fluoropyrimidine medications include the following:

• 5-fluorouracil (also known as 5-FU or Adrucil^®) may be given alone or combined with other chemotherapy drugs in a regimen such as FOLFOX, FOLFIRI, FOLFIRINOX, or FLOT.
• Capecitabine (also known as Xeloda^®) may be given alone or combined with other chemotherapy drugs in a regimen such as CAPOX or XELOX, CAPIRI, or CAPOXIRI.

The DPYD gene provides instructions for making an enzyme called dihydropyrimidine dehydrogenase (DPD). This enzyme is responsible for breaking down fluoropyrimidines and eliminating the drug from your body. This process helps to prevent drug toxicities. DPYD genotyping is a type of genetic test that finds out if you have a genetic variant that causes DPD deficiency (reduced or absent enzyme activity).

A person with DPD deficiency cannot break down fluoropyrimidines normally, which can result in a buildup of drug in the body. Individuals with DPD deficiency have an increased risk of severe, and sometimes life-threatening, side effects.

Fluoropyrimidine side effects due to DPD deficiency can occur very early in treatment or during the first few months of therapy. Some of these serious side effects include low blood counts called neutropenia, severe diarrhea, and blistering of the mouth, hands, or feet. Your medical team can make changes to your treatment if DPYD genotyping shows you have DPD deficiency.

In most instances, a reduction in fluoropyrimidine dose can help prevent severe toxicities for those with DPD deficiency. In certain instances, your medical team may prefer to avoid fluoropyrimidines.  

Your medical team will collect a blood sample and send it to the laboratory for DPYD genotyping. Results are usually available in one or two weeks.

If DPYD genotyping shows you have DPD deficiency, consider the following actions:

• Notify your other healthcare provider(s), especially if you are getting care outside of Moffitt.
• Share your DPYD test result with the Emergency Department and/or Urgent Care providers in the event you need to seek care at those facilities after receiving chemotherapy.
• Be familiar with the side effects of chemotherapy toxicity (see below) and report them immediately to your healthcare team.
• Since DPD deficiency can run in the family, consider sharing this information with family members in case they are ever diagnosed with a cancer that requires treatment with a fluoropyrimidine. They can also undergo DPYD genotyping to see if they have DPD deficiency.

Contact your medical team immediately for any of the following signs and symptoms of fluoropyrimidine toxicity:

• Diarrhea that occurs 4 to 6 or more times above your daily baseline.
• Nausea that is severe enough to cause you to eat less than normal.
• Vomiting 3 to 5 or more times in a day.
• Pain, swelling, blisters or ulcers in your mouth or on your lips that are severe enough to interfere with eating.

Other signs and symptoms that can occur include, but are not limited to:

• Low blood counts called neutropenia, which can put you at risk of infection, anemia, and/or bleeding.
• Cardiac complications such as irregular heart rhythms and heart failure.

These side effects can be more severe and sometimes life-threatening in a person with DPD deficiency. Additionally, these side effects may happen in the early stages of treatment or weeks after starting fluoropyrimidine therapy.

Your medical team may prescribe the planned dose of 5-FU or capecitabine if DPYD genotyping shows that you have normal DPD enzyme activity. Keep in mind that even if DPYD genotyping shows you do not have DPD deficiency, some people may still develop serious side effects.  A limitation to DPYD genotyping is that you might have a mutation that the laboratory does not test for or a rare mutation that we do not know about yet.

The coverage policies for DPYD genotyping vary across different health insurance providers. Many healthcare policies include coverage for DPYD genotyping. In general, DPYD genotyping is reimbursed by Medicare in most U.S. states and a growing number of private insurance companies. Contact your insurance provider to find out if DPYD genotyping is a covered benefit. On average, the out-of-pocket cost for DPYD genotyping may be around $250 to $500 if it is not covered by your insurance.

Consider these talking points and questions to ask your provider:

• I am interested in DPYD genotyping. When should this test be performed, and how long will it take to get the results? 
• How will the results of this test affect my specific chemotherapy plan?
• Are there alternative treatment options available if I am found to have DPD deficiency, and are those treatments well-suited for my type of cancer?
• I have a DPD deficiency and I decided to undergo fluoropyrimidine treatment. What are the plans for monitoring my response to chemotherapy?
• What are my options for adjusting the dosage or frequency of my chemotherapy, based on how I respond to my treatment?

For more information about DPYD genotyping and your cancer, here are some additional resources:

• FDA labeling for capecitabine (see section on Patient Information, page 49) 
• FDA labeling for fluorouracil (see section on Patient Counseling Information, page 13)
• DPYD Gene