UGT1A1 Genetic Testing to Guide Irinotecan Dosing

Irinotecan is a chemotherapy medication used to treat certain cancers. Irinotecan may be given alone or combined with other chemotherapy drugs in a regimen such as FOLFIRI, FOLFIRINOX, CAPIRI, or CAPOXIRI. Your body changes irinotecan into a stronger form (called SN-38) to fight cancer, but it can cause side effects if it stays in the body too long.

The UGT1A1 gene provides instructions for making an enzyme called uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). This enzyme helps your body safely process irinotecan. UGT1A1 genetic testing is done to find out if you have changes in the gene that cause reduced enzyme activity.

UGT1A1 genetic testing can let you know how well you tolerate irinotecan. If your test result shows that you process the drug more slowly than typical (called UGT1A1 poor metabolizer), you may be at higher risk of experiencing serious side effects. Some of these serious side effects include low blood counts called neutropenia and severe diarrhea. Your medical team can make changes to your dose of irinotecan based on your UGT1A1 test results. In most instances, lowering the irinotecan dose can help prevent severe toxicities.

Your medical team will collect a blood sample and send it to the laboratory for UGT1A1 genetic testing. Results are usually available in one or two weeks.

If UGT1A1 genetic testing shows you are a UGT1A1 poor metabolizer, consider the following actions:

• Notify your other healthcare provider(s), especially if you are getting care outside of Moffitt.
• Share your UGT1A1 test result to the Emergency Department and/or Urgent Care providers in the event you need to seek care at those facilities after receiving irinotecan.
• Be familiar with the side effects of irinotecan toxicity (see below) and report them immediately to your healthcare team.
• Since UGT1A1 poor metabolism can run in the family, consider sharing this information with family members in case they are diagnosed with a cancer that requires treatment with irinotecan. They can also undergo UGT1A1 genetic testing to see if they are a UGT1A1 poor metabolizer.

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

• Diarrhea for the first time during treatment
• Diarrhea not under control within 24 hours
• Black or bloody stools
• Nausea or vomiting that makes you unable to take fluids by mouth
• Dehydration from too much fluid loss, such as lightheadedness, dizziness, fainting, decreased urination, dry mouth, and wrinkled skin

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

• Low blood counts, called neutropenia, can put you at risk of infection, anemia, and/or bleeding.

Your medical team may prescribe the planned dose of irinotecan if UGT1A1 testing shows that you have normal UGT1A1 enzyme activity. Keep in mind that even if testing shows you do not have UGT1A1 poor metabolism, some people may still develop serious side effects. A limitation to UGT1A1 genetic testing 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 UGT1A1 genetic testing vary across different health insurance providers. Many healthcare policies include coverage for UGT1A1 genetic testing. In general, UGT1A1 genetic testing is reimbursed by Medicare in most US states and a growing number of private insurance companies. Contact your insurance provider to find out if UGT1A1 genetic testing is a covered benefit. On average, the out-of-pocket cost for UGT1A1 genetic testing may be around $250 to $500 if it is not covered by your insurance.

UGT1A1 test results can also provide helpful information on whether you have Gilbert’s syndrome. Gilbert syndrome is a benign liver condition in which the liver cannot properly process bilirubin, which comes from normal red blood cells.

Consider these talking points and questions to ask your provider:

• I am interested in UGT1A1 genetic testing. 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?
• I am a UGT1A1 poor metabolizer, and I decided to undergo treatment with irinotecan. 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?