The need for pretreatment DPYD genotyping
June 2025—I was encouraged to read the CAP TODAY articles on DPYD testing (“Time for wider pretreatment DPYD genotyping?” December 2024; “DPYD genotyping assays—what’s recommended and why,” January 2025). I lost my mother not to her cancer but to a known and preventable toxicity from 5-fluorouracil (5-FU) chemotherapy. She was never informed of the risks of 5-FU if one is DPD deficient nor was she tested for DPD deficiency, a genetic condition that impairs the body’s ability to break down 5-FU and capecitabine. Within days of starting treatment, she developed devastating toxicity that ultimately took her life. We had no warning. Only after she was suffering in the hospital from 5-FU toxicity did I learn about DPYD testing, which could have spared her horrific pain and saved her life. My mom was so easy to live with and so hard to live without. We continue to be heartbroken that her golden years were cut short.
My mother’s story is not as rare as we once thought. DPD deficiency is present in an estimated five to eight percent of the population. In the United States, this translates to an estimated 700 to 1,400 patients dying each year from 5-FU toxicity owing to undetected DPD deficiency. These are mothers, fathers, spouses, and children—lives cut short not by cancer but by a toxic reaction to a medication that could have been avoided. The suffering extends beyond those we lose: Countless others endure horrific, disabling side effects and prolonged hospitalizations when a simple test could have spared them.
It is agonizing to know that my mother’s death, and that of so many others, did not have to happen. A DPYD genetic test before starting 5-FU or capecitabine could have revealed her DPD deficiency. Had we known, her doctors could have adjusted her chemotherapy dose or chosen a different treatment and likely prevented the toxicity that killed her. In the wake of this loss, I co-founded Advocates for Universal DPD/DPYD Testing (AUDT) with others who share the same heartache and similarly tragic stories of pain, suffering, and death. We are patients and families advocating for pretreatment DPYD genetic testing to be the standard of care in the U.S., just as it is in the European Union, United Kingdom, Australia, and much of Canada. It’s common sense. It saves lives. And it prevents suffering. No family should have to experience this preventable loss.
As Daniel Hertz, PharmD, PhD, explained in your December article, patients with DPYD variants face a 70 percent risk of severe toxicity and a three percent risk of death if treated with standard doses of fluoropyrimidines. At Atrium Health Levine Cancer, the team of Jai N. Patel, PharmD, found that pretreatment testing reduced hospitalizations and brought toxicity levels down to those of noncarriers—essentially normalizing risk. These are real-world results with real lives on the line. Simply put, testing works: It keeps patients safe.
The January article further highlighted the variability in commercial tests and emphasized the importance of comprehensive genotyping. Reynold Ly, PhD, of Nationwide Children’s Hospital made it clear: When patients with reduced or no DPD enzyme activity receive standard doses of 5-FU, toxicity increases dramatically. That is exactly what happened to my mother.
There are cancer centers in the U.S. that have implemented pretreatment DPYD testing, among them Atrium Health Levine Cancer and Duke Cancer Center and the cancer centers of St. Elizabeth Health. The U.S. Veterans Affairs also implemented pretreatment testing. The tools are available. The data is clear. The cost is justified, and the human cost of inaction is staggering. Pretreatment DPYD testing does not limit care—it enables safe, effective treatment. As Dr. Hertz noted, “We have a demonstrated clinical benefit with no countervailing demonstrated risk.”
Despite the evidence shared in these articles, most patients in the U.S. still are not offered testing. And patients are not being informed of the risks of fluoropyrimidine chemotherapy if they happen to be DPD deficient. The Jan. 24, 2025 Food and Drug Administration safety announcement reinforced the patient safety labeling changes to capecitabine (December 2022) and fluorouracil (March 2024). The safety announcement reinforced the need for clinician awareness of the risks of DPD deficiency and to inform patients about the serious and life-threatening risks of DPD deficiency and to discuss DPYD testing with patients. In March 2025, the National Comprehensive Cancer Network updated guidelines to suggest DPYD testing for gastrointestinal cancers. From a patient advocate perspective, a suggestion is not enough. We need a recommendation for universal pretreatment testing—before any fluoropyrimidine chemotherapy begins—at every cancer center in the United States. Implementing universal DPD deficiency testing is a clear, attainable step toward safer cancer care.
I implore the health care community to treat DPYD testing as an immediate life-saving intervention that should be offered to every patient before they begin 5-FU or capecitabine chemotherapy. How many more individuals must be lost before we protect patients from this known danger?
Karen Merritt
Co-founder
Advocates for Universal DPD/DPYD Testing
Chelan, Wash.
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