Guideline: FDA recommends testing to prevent serious side effects from 5-FU and capecitabine chemotherapy

RELEVANCE

Most relevant for: People diagnosed with cancer who require 5-FU or capecitabine treatment.

It may also be relevant for:

• men with breast cancer
• people with colorectal cancer
• people with pancreatic cancer
• people with metastatic or advanced cancer

Relevance: High

Research Timeline: Post Approval

More rating details

What is this guideline about?

Capecitabine (Xeloda) and 5-FU (fluorouracil) are two related chemotherapy drugs used to treat several different types of cancer, including anal, breast, colon, gastric, pancreatic and rectal cancers. Some people have changes in a gene called DPYD that slow their ability to break down 5-FU and capecitabine. The buildup of these drugs in the body can increase the risk of serious side effects. People with these gene changes are more likely to experience side effects from these drugs. On very rare occasions, this can result in very serious side effects or even death. DPYD genetic testing (also called DPD testing) can help identify people with these gene changes before chemotherapy begins.

In October 2025, the FDA added a black box warning to the drug labels for 5-FU and capecitabine. (Black box warnings are the strongest safety warning the agency issues to alert people about serious side effects and safety risks.) This warning recommends DPYD testing of patients before they receive the drugs, except in emergencies when treatment cannot be delayed. Professional organizations, including the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), have begun adding DPYD testing recommendations to their guidelines.

Why is this guideline important?

Testing for changes in the DPYD gene can identify people who are most likely to have serious side effects from Xeloda or 5‑FU. When doctors can identify these patients before treatment starts, they can lower the dose or choose a different drug. This can help prevent death or severe side effects, reduce hospital stays, decrease the chance that patients will need to stop or delay treatment and reduce patient discomfort while undergoing treatment.

How does DPYD testing work?

Oncologists usually order DPYD testing before chemotherapy begins. Testing involves a simple blood draw or cheek swab. A laboratory then analyzes the sample for known changes in the DPYD gene that are linked to reduced DPYD activity, and provides results that help oncologists understand how quickly or slowly a patient’s body can break down 5-FU and capecitabine. Test results may take between 5-10 days.

Based on DYPD testing results, patients are categorized by how well they are predicted to break down (metabolize) capecitabine and 5-FU:

• Normal metabolizer—A person who breaks down the drugs at the expected rate.
• Intermediate metabolizer—A person whose ability to break down the drugs is reduced/slower than what is expected.
• Poor metabolizer—A person with a severely reduced ability to metabolize 5-FU and capecitabine. This result is rare.

These categories help guide chemotherapy dosing.

More insurance companies are covering the costs of this testing as it is added to professional guidelines.

Limitations of DPYD testing

DPYD testing is a helpful tool to improve the safety of 5-FU and capecitabine chemotherapy, but the test has some limitations:

• A normal test doesn’t guarantee that people won’t have side effects from the drugs.
  • The test can identify the most common DPYD gene changes, but not all of the possible harmful changes. Some poor metabolizers may not be identified through testing.
  • Other factors affect treatment side effects, including organ function, drug interactions, patient age and the influence of other genes.
• No single test has been approved by the FDA. Most testing is performed with high-quality laboratory-developed tests, but tests and results vary between labs.
• Although experts widely agree about avoiding 5-FU or capecitabine in people who fall into the poor metabolism range, they don’t universally agree on the best way to manage people whose results are in the intermediate range. Dosing decisions are based on the needs of individual patients, with involvement by their oncologist.
• Depending on the lab, waiting times for test results could delay the start of treatment. In these situations, it’s important for patients to talk with their oncologist to understand their treatment options as well as the risks and benefits of different options.
• Pharmacogenomics (how genes affect people’s response to medications) is a growing field in cancer medicine. Not all doctors are familiar with using genetic tests to monitor how genes interact with treatment.

Despite these limits, many experts consider the incorporation of DPYD testing into guidelines a major improvement in cancer patient safety.

What does this mean for me?

Although rare, certain changes in the DPYD gene can put people at risk for increased side effects to 5-FU or capecitabine chemotherapy. If you have been diagnosed with cancer, and 5-FU or capecitabine are part of your treatment plan, ask your doctor about DPYD testing. If your doctor is not familiar with testing, you may be able to request a telehealth referral to a genetic counseling practice with expertise in pharmacogenomics. Some labs offer rapid turnaround times, which may still take a week or more for results. Results can help doctors decide on the safest chemotherapy options for you.

References

U.S. Food and Drug Administration. Safety labeling update for capecitabine and fluorouracil (5-FU) on risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency Posted Feb 5, 2026. Accessed February 10, 2026.

ASCO Connection. ASCO Clinical Notice: Reaffirming the Necessity for DPYD Genotyping in Fluoropyrimidine Therapy. Posted January 22, 2026. Accessed February 10, 2026.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 2/11/26