DPD Deficiency for 5-FU Response

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DPD Deficiency for 5-FU Response

What Affects 5-Fluorouracil Drug Response?

Changes in the gene called DPYD may affect how a person responds to 5-FU. This gene makes an enzyme called dihydropyrimidine dehydrogenase, or DPD. An enzyme converts one chemical to another. When you take a drug, it may need to be converted to other chemicals through a series of enzymes before your body can use it. DPD deficiency is not the only cause of toxic reactions to 5-FU. Other enzymes have been linked to toxicity, but only some are well known and available for testing.

DPD

The DPD enzyme helps your body process 5-FU. It is the first enzyme in the process that breaks down 5-FU. The DPD enzyme is responsible for breaking down about 80% of 5-FU. Changes in the DPYD gene can cause the enzyme not to work, or not to work as well. When this happens, more 5-FU stays in your body for longer than expected. This may be one reason for side effects. About 1% of people who take 5-FU have severe DPD deficiency (abnormally low levels of DPD).

About 92% of people have normal DPD activity. They metabolize 5-FU in the way doctors usually predict. This means that they can take the usual dose of the drug. Though side effects are possible, the chances for side effects are lower.

Up to 7% of people have one normal DPYD gene and one gene variant. They have lower activity and they metabolize 5-FU more slowly. They can usually still take the drug but may need to start out at half the usual dose.

Up to 1% of people have two gene variants. They have low or no DPD activity. They metabolize 5-FU very slowly. Not having enough of the DPD enzyme has been strongly associated with developing severe side effects and 5-FU toxicity. People who have low levels of DPD should not take 5-FU.


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Other Factors

DPYD gene changes alone do not explain all the differences in how people respond to 5-FU therapy. There are other genes involved in breaking down 5-FU. There are other factors, like overall health and other medicines, that change how people respond to 5-FU. You should discuss any medications or vaccinations that you are taking or plan to take with your physician.

Next: Who Should Consider Testing for DPD Deficiency?

Why are you considering DPD deficiency testing for 5-FU response?

I am considering starting 5-FU to treat a medical condition.

I am currently taking/using 5-FU and I'm not having any problems with it.

I am currently taking/using 5-FU and I'm having side effects.

None of these

DPD deficiency testing for 5-FU response may be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency before this drug is prescribed. At this point, the testing decision is left up to the doctor and the patient.

You should talk to your doctor to learn if DPD deficiency testing would make a difference for your healthcare. The table below sums up how test results may change your care.

Test Result Chance To Get This Result
What This Result Means
Normal DPD ~92%
  • You metabolize the drug normally.
  • You have a lower chance for side effects.
  • You can take the usual dose of the drug.
Intermediate DPD ~7%
  • You metabolize the drug more slowly.
  • You may have a higher chance for side effects.
  • Most people with this result can still take 5-FU, but should start with half the usual dose.
Low or absent DPD~1%
  • You cannot effectively metabolize this drug.
  • You have a high risk of toxic side effects.
  • You should not take this drug. Your doctor may consider a different treatment for you.

DPD deficiency testing for 5-FU response may not be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency when this drug is prescribed. At this point, the testing decision is left up to the doctor and the patient.

Most people who have DPD deficiency will show signs of 5-FU toxicity after the first treatment. Since you are taking/using the drug without any side effects, testing at this point is probably not that helpful for you. You should continue to be monitored for side effects like everyone else who takes/uses 5-FU. Be sure to mention any concerns or issues you might be having with your doctor immediately.

DPD deficiency testing for 5-FU response may be useful for you. Some people have an increased sensitivity to 5-FU and are at risk for severe side effects. People with a known DPD deficiency (not enough DPD enzyme) should not take 5-FU. People who develop symptoms of DPD deficiency while taking 5-FU should stop taking it. However, the FDA does not require or recommend testing for DPD deficiency when this drug is prescribed. Some doctors may decide that testing is useful to find out if DPD deficiency explains your side effects.

  • If testing finds two gene variants and/or low-to-absent levels of DPD, you have high risk for drug toxicity. You should not take 5-FU. These results likely explain your side effects. Your doctor may want to try a different treatment.
  • If testing finds a gene variant and/or intermediate levels of DPD, you may have a higher risk for drug toxicity, but you may be able to tolerate a lowered dose. Your doctor may try lowering your dose, or your doctor may talk to you about changing to a different treatment.
  • If your test results are normal, DPD deficiency is not likely the cause of your side effects. Other factors may be affecting the way you break down this drug. Your doctor will have to make a decision about whether to lower your dose or change to a different drug therapy by weighing the benefits you are getting against the side effects.

DPD deficiency testing for 5-FU response may not be useful for you. Testing is not recommended for people who aren't starting or currently taking 5-FU. See Who Should Consider Testing for the main reasons for testing.

If you have a reason for testing that isn't covered here, talk to your doctor or a genetic counselor about whether testing might be useful for you.