Honoring Maura: Understanding the link between DPD deficiency and a chemotherapy drug’s side effects

Katie’s mother had a rare genetic disorder called dihydropyrimidine dehydrogenase (DPD) deficiency that she wasn’t aware of because she had never experienced any symptoms of the genetic mutation. Katie learned this particular genetic disorder can have harmful consequences for people taking a certain chemotherapy drug. For Maura, this discovery was made too late. Katie urges people living with breast cancer, and those who care for them, to advocate for themselves and for those they love, especially when something doesn’t feel right.

“My mom was a beacon of positivity.”

Katie’s mother often marveled at how healthy she felt during most of the 5 years she lived with MBC (stage IV breast cancer). She maintained a daily walking routine, volunteered for causes she cared deeply about, and enjoyed spending time with her husband and her children, as well as her friends. She hosted dinner parties and enjoyed sleepovers with her first grandchild at her home in St. Paul, Minnesota.

Maura had retired as a reading teacher for students with learning disabilities in June 2019 at age 62. Later that month, a routine screening mammogram revealed a mass that looked suspicious. Additional tests confirmed a diagnosis of invasive lobular carcinoma. In August of that year, Maura had a bilateral (double) mastectomy. Shortly thereafter, her care team discovered cancer had metastasized to her bones.

“It was a really devastating time,” says Katie. “But my mom was a beacon of hope and positivity.” She was determined to “live her life to the fullest.”

Maura’s treatment included hormonal therapy, targeted therapy, and chemotherapy. Although she had some chemo-related side effects like occasional vomiting and diarrhea, Katie says her mother “was still feeling really good.” In the summer of 2023, she reached a disease-stable period, during which she was able to pause treatment.

Unusual side effects

Katie was perplexed when her mother’s physical and cognitive health declined dramatically and rapidly in the spring of 2024. Maura’s care team started her on the chemotherapy drug capecitabine (Xeloda) in combination with two other drugs that spring because the cancer had progressed. Maura experienced some diarrhea, a common side effect of capecitabine, but her digestive issues worsened. She had bouts of vomiting, and began to stop eating and drinking; as a result, she became dehydrated. “I was really worried that she was getting so weak,” says Katie, “and that her immune system wouldn’t be able to fight the cancer.” Assuming Maura’s  symptoms were side effects of the capecitabine, her care team and family agreed that she needed to take a break from that medicine for a week and then reassess.   

But pausing treatment did not help to improve Maura’s symptoms, which included mucositis (sores in her mouth) and difficulty swallowing. She developed neutropenia (low levels of white blood cells), which makes it hard for the body to fight infection, a pulmonary embolism (blood clot in her lung), tachycardia (increased heart rate), and encephalopathy (dysfunction of the brain).   

Katie and her mother’s care team were baffled, Katie remembers. “Her cancer hadn’t grown, and they couldn’t figure out why she wasn’t responding to supportive care,” she recalls. “I didn’t know what was happening to her.” Katie asked her mother’s doctors and nurses questions to try to make sense of it, and they gently reminded her: “Your mother does have MBC.” Feeling frustrated, Katie began doing online research to see if she could find any information about capecitabine and the side effects that were harming her mother. 

Here's what she discovered: People who have DPD deficiency are at increased risk for severe reactions (like the ones Katie was witnessing) when taking capecitabine — as well as treatment-related death. Katie learned that a medicine, uridine triacetate, can stop capecitabine’s adverse effects if taken within 4 days of taking capecitabine. Maura had not been tested for DPD deficiency before her diagnosis or starting capecitabine, but Katie urged her mother’s care team to order the antidote — and they did. Sadly, Maura died before they received and could administer it.  

What is DPD deficiency?

DPD deficiency is a condition that can cause serious brain and movement problems. It is usually diagnosed in infants.

However, most people who have DPD deficiency have no signs or symptoms of disease; in these people, the only way to diagnosis DPD deficiency is by lab testing. After Maura’s death, Katie had her mother tested for the genetic disorder, and Maura did have it. Capecitabine’s prescribing information outlines the risks of administering the drug to someone who has DPD deficiency. People with no symptoms, like Maura, would most likely not have been tested for the deficiency as they may not know they had it.

Because DPD deficiency is inherited, Katie and her sister most likely also have the disorder, Katie’s been told. Katie plans to get tested.

Self-advocacy and a strong support system

If you ask Katie what she would tell people recently diagnosed with breast cancer, she will say, “Advocating for themselves is the most important job they have.” She recommends:

• Have open, honest conversations with your cancer care team.
• Ask your doctor questions about treatment options, and what the risks are.
• Ask your doctors if they have had experience prescribing the type of chemotherapy or other medicine they suggest for you.
• Don’t be afraid to do your own research.
• Take notes and write down questions so you can follow up with your care team.
• Have loved ones advocate for you, if possible.

The prescribing information for capecitabine mentions the severe risks associated with taking the drug and DPD deficiency, and that “testing should be considered.” The U.S. Food and Drug Administration encourages doctors to discuss testing for DPD deficiency with patients before prescribing capecitabine, but mandatory testing guidelines do not exist in the U.S.

“These risks need to be shared with patients and their families,” says Katie. “They deserve to know.”

“Don’t lose hope.”

Katie hopes people whose lives are impacted by cancer remain positive and hopeful like Maura. There are so many new treatments and new ways to help people.”

Katie says her desire to share Maura’s experience with capecitabine and DPD deficiency has helped her manage the weight of her grief, reclaim a sense of hopefulness, and honor her mother’s zest for life and devotion to helping others. “My mom would want me to use her story to save other people from having the same tragic outcome.”