UGT1A1 Testing for Irinotecan Response

Is Testing Right for Me? I Have My Test Results

UGT1A1 Testing for Irinotecan Response

  • Author: Nicole Teed, MS, CGC; Lisa Lee
  • Reviewer: Julie Pippins, PharmD
  • Last updated: 2011-11-28

What Is Irinotecan?

Irinotecan (Camptosar®) (pronounced eye-rin-oh-tee-kan) is an anti-cancer chemotherapy drug. It is often used along with other chemotherapy agents to treat people who have metastatic colorectal cancer, or cancer that has spread to other parts of the body.

When cells in our body divide in two, the DNA breaks and then is fixed. Irinotecan works by preventing the DNA from being fixed, which kills the cell. Since cancer cells grow and divide faster than normal cells, cancer cells are more likely to be killed by irinotecan than healthy cells.

Irinotecan is sometimes used together with another chemotherapy drug called 5-FU (5-fluorouracil). Genetic changes can also affect how you react to 5-FU. (Read more: 5-FU.)

Irinotecan is approved to treat:

  • Metastatic colorectal cancer – cancer that has spread to other parts of the body
  • Recurrent metastatic colorectal cancer – cancer that has come back

Some doctors also use irinotecan to treat other types of cancer, such as lung cancer and ovarian cancer.

Irinotecan can cause side effects. Common side effects include:

  • Diarrhea
  • Neutropenia: low levels of white blood cells that can lead to life-threatening infections
  • Nausea or vomiting
  • Abdominal pain, not feeling hungry
  • Hair loss
  • Feeling weak
Next: What Affects Irinotecan Drug Response?

Why are you considering UGT1A1 testing for irinotecan response?

I'm considering starting irinotecan to treat colorectal cancer.

I'm taking irinotecan and I'm not having any problems with it.

I'm taking irinotecan and I'm having side effects.

None of these.

UGT1A1 testing for irinotecan response may be useful for you. The package insert for irinotecan approved by the U.S. Food and Drug Administration (FDA) says that lower starting doses of irinotecan should be considered for people who have two UGT1A1*28 variants to help prevent severe side effects. While the FDA doesn't require or recommend testing, they consider it an "approved biomarker" and have used UGT1A1 as an example of genetic testing for drug response. They have also approved a test kit for labs to use to perform testing.

In their 2012 clinical practice guidelines, the National Comprehensive Cancer Network says that testing may be useful but that guidelines for use haven’t been established yet. In 2009 an expert group from the Centers for Disease Control and Prevention, called EGAPP, said that research had not yet shown whether testing is useful or not. Since 2009, several new studies have been published that show that people who have a UGT1A1*28 gene variant have a higher chance of having serious side effects from irinotecan. At this point, the testing decision is left up to the doctor and the patient.

You should talk to your doctor to learn if UGT1A1 testing could help your healthcare. The table below sums up how test results may change your care.

Possible Test Results and What They Mean

Test Result Chance To Get This Result
What This Result Means
Normal UGT1A1 ~45%
  • You metabolize the drug normally.
  • You have a lower chance for side effects.
  • You can take the usual dose of the drug.
Intermediate UGT1A1 ~45%
  • You metabolize the drug more slowly.
  • You may have a higher chance for side effects.
  • Most people with this result can still start the drug at the usual dose.
Low or absent UGT1A1
~10%
  • You have a higher risk for side effects.
  • Your doctor may consider using a different drug regimen.
  • If you take this drug, you'll need a smaller dose.  Your doctor will monitor you carefully for side effects.

UGT1A1 testing for irinotecan response may not be useful for you. The prescribing information for irinotecan approved by the U.S. Food and Drug Administration (FDA) says that lower starting doses of irinotecan should be considered for people who have two UGT1A1*28 variants to help prevent severe side effects. While the FDA doesn't require or recommend testing, they consider it an "approved biomarker" and have used UGT1A1 as an example of genetic testing for drug response. They have also approved a test kit for labs to use to perform testing.

In their 2012 clinical practice guidelines, the National Comprehensive Cancer Network recognizes how testing can be used, but says that guidelines for use haven't been established yet. They add that once a person has been on irinotecan, changes in dose should be based on their response, not genetic test results. 

Since you are taking the drug without any side effects, testing at this point isn't helpful. You should be monitored for side effects like everyone else who takes irinotecan. The most common serious side effect of irinotecan therapy is a low blood count. Your doctor can check for this with routine lab testing.

UGT1A1 testing for irinotecan response may not be useful for you. In their 2012 clinical practice guidelines, the National Comprehensive Cancer Network says, "testing on a patient who has experienced irinotecan toxicity is not recommended since that patient will require a dose reduction regardless of the UGT1A1 test result."

Some doctors may decide that testing is useful to find out whether a gene variant may help explain your side effects.

  • If testing finds two gene variants, you have a higher risk for drug toxicity. These results explain why you are having side effects from the drug. Your doctor may talk to you about changing to a different treatment.
  • If testing finds one gene variant, 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 switching to a different treatment.
  • If your test results are normal, changes in the UGT1A1 gene do not explain why you are having side effects. Other factors can affect the way you metabolize this drug. Your doctor will have to make a decision about whether to lower your dose or change to a different drug by weighing the benefits you are getting against the side effects.

UGT1A1 testing for irinotecan response may not be useful for you. The main reasons for testing are listed in the Who Should Consider Testing section. Testing is not recommended for people who aren't starting or currently taking irinotecan.

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.