Research and Advocacy Pays Off in an FDA Action That Will Save Lives

Ann Arbor–A common cancer treatment can be toxic or fatal for patients who carry variants of a specific gene. Now, to improve safety, all patients are recommended to be tested for the variants before taking the drug, thanks in large part to the research and advocacy of Daniel Hertz, PharmD, PhD, Associate Professor of Clinical Pharmacy at the University of Michigan College of Pharmacy, U-M Rogel Scholar and colleagues at the College and University of Michigan, Rogel Cancer Center and the Institute for Healthcare Policy and Innovation.

On Oct. 3, 2025, the US Food and Drug Administration adopted a new label on capecitabine (Xeloda) that includes a boxed warning to “test patients for genetic variants of DPYD (dihydropyrimidine dehydrogenase) prior to initiating Xeloda, unless immediate treatment is necessary.”

Oncologists prescribe capecitabine, a fluoropyrimidine-based chemotherapy, to treat colorectal, head and neck, and sometimes breast cancers. A gene called DPYD makes an enzyme that removes the drug from the body.

According to the Journal of Clinical Oncology, approximately 7% of the population has one of four identified variants in DPYD that cause them to break down fluoropyrimidine chemotherapy more slowly. Those with a variant face a 60% to 70% chance of experiencing a severe toxic reaction with standard treatment. About 30% will require hospitalization for the toxic response; 2% to 3% will die. About 250,000 cancer patients are treated with fluoropyrimidine-based drugs annually, and an estimated 1,300 patients die annually from this toxic reaction.

“We’re excited that the FDA has taken this action to require testing and enhance the safety of treatment for tens of thousands of patients,” said Hertz.

“The impact the FDA’s decision has on patients’ lives ensures an improved standard of care that can save their lives and prevent unnecessary hospitalizations,” states Vicki Ellingrod, Dean of the College of Pharmacy.

The link between the genetic variant and toxicity was identified decades ago. A blood test that costs about $250 can identify those who carry the variant, so that treatment can be modified to reduce the risk of a toxic reaction. Hertz collaborated with Dan Hayes, Professor of Breast Cancer Research at Rogel Cancer Center, who has been a pioneer in developing the framework for demonstrating the clinical utility of biomarkers, and with whom Dr. Hertz worked to create a similar framework for genetic biomarkers of treatment-related toxicity, including DPYD.

Working with colleagues at the College of Pharmacy and Rogel Cancer Center, Hertz confirmed the efficacy of DPYD testing by developing a screening system that tapped into a unique genetic database at Michigan Medicine, identified patients suspected of carrying variants, and triggered genetic testing to confirm their status. This proactive action prevented patients from receiving toxic treatment.

Hertz has become one of the most prominent advocates for universal DPYD testing and labeling fluoropyrimidine-based drugs to require such tests. He serves as an unpaid medical adviser with Advocates for Universal DPD/DPYD Testing, a group founded by surviving family members with a loved one who suffered and died from severe toxicity. He has worked to persuade the National Comprehensive Cancer Network and other oncology medical organizations to incorporate testing in treatment guidelines for this class of drugs. He petitioned the FDA to require labeling that alerts clinicians to the risks and presented at a conference hosted by the FDA in January 2025 to reiterate concerns and the need for testing.

When he learned in early October that the FDA had changed the drug label, he was thrilled. “It feels like six years of work I’ve done, that patients, families, and other researchers have done, has finally paid off. The FDA now says, explicitly and unequivocally, that genetic testing should be conducted before initiating treatment. I’m especially grateful to my colleagues and the advocacy group whose passion and dedication were invaluable in achieving this long-sought-after outcome.”

Another drug in this class, 5-fluorouracil (5-FU), causes the same toxicity for those with the DPYD variant. Hertz is hopeful the FDA will make a similar change to the 5-FU label soon.

“It’s an exciting space to work in because we can see the immediate effects of things we’re doing and know that this will make a difference for tens of thousands of patients and save hundreds of lives.”

This article is reprinted with permission of the University of Michigan College of Pharmacy. The author is Lindsay Groth, Executive Director of Marketing and Communications, [email protected]

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