Chemo May Kill Without This Test First: Why DPYD Screening Should Be Mandatory
One woman’s death sparks fresh urgency for genetic testing before common chemotherapy drugs like 5-FU and capecitabine
Topline
Routine genetic testing before starting chemotherapy with capecitabine or 5-FU could prevent hundreds of avoidable deaths each year. Yet most patients in the U.S. still begin treatment without being screened for DPD enzyme deficiency, a known risk factor for life-threatening toxicity.
Study Details
The issue came to national attention after the death of JoEllen Zembruski-Ruple, a 65-year-old patient advocate who died in March 2025 after just eight days on capecitabine. She had an inherited deficiency in the DPD enzyme (encoded by the DPYD gene), which is responsible for metabolizing these common cancer drugs. Without the enzyme, the medication builds up to toxic levels in the body.
An estimated 1,300 Americans die every year from similar chemotherapy reactions most of them never knew they carried a dangerous gene variant.
Methodology
The evidence supporting DPYD testing is strong.
Large studies show 8–10% of people carry at least one risky variant.
If detected in advance, doses can be reduced or alternative drugs can be used.
Recent trials and health system data show lower toxicity and no loss in cancer control when patients are dosed according to their genetic profile.
Results from DPYD tests can be available in 2–3 days and now cost under $300, but testing remains optional.
Key Findings
Untested patients are at risk: Nearly all deaths from capecitabine or 5-FU could be prevented with upfront screening.
A test exists and works: Identifying gene variants can guide doctors to lower initial doses, especially for those with one or two high-risk copies.
Delayed action from top cancer centers: Until March 2025, major cancer guidelines didn’t recommend testing. That is now beginning to change, but many providers still don’t offer it.
Patients who insist may survive: One woman refused to start capecitabine until she got tested. Her result showed a high-risk gene, and her doctors lowered the dose. That likely saved her life.
Implications for Practice
For patients:
Ask your doctor before starting 5-FU or capecitabine: “Have I been tested for DPD deficiency?” If not, demand it. If your insurer won’t pay, it could still be worth it out of pocket.
For oncologists:
The cost of a DPYD test is far less than the cost of treating neutropenia, mucositis, or worse death. Personalized dosing is not just safer, it’s more ethical.
For hospital systems:
Include DPYD genotyping in pre-chemo panels. Make it default. Document discussions. Track results.
For health policymakers:
Reimbursement and regulatory frameworks must align with NCCN’s March 2025 update. Every preventable death is a system failure.