# Advocates for Universal DPD/DPYD Testing (AUDT)

> AUDT is a 501(c)(3) non-profit organization of patient advocates and medical professionals working to improve the standard of care for cancer patients undergoing fluoropyrimidine chemotherapy (5-FU and/or Capecitabine), through advocacy, education, and research. Their mission is to ensure universal pre-treatment DPYD genetic testing to prevent severe toxicity and death.

## Site Overview

- [Homepage](https://test4dpd.org/): Overview of the DPD/DPYD testing issue, FDA Black Box Warning (issued October 3, 2025), key statistics, patient toolkit, and clinician resources.
- [Why Test](https://test4dpd.org/why-test/): Explains DPD deficiency, the genetic basis (DPYD variants), risk statistics, how to get tested, and how to interpret results.
- [Working with Your Oncologist](https://test4dpd.org/why-test/working-with-your-oncologist/): Guidance for patients on initiating testing discussions with their oncologist.
- [Evidence of Test Benefits](https://test4dpd.org/why-test/evidence-of-test-benefits/): Clinical evidence supporting pre-treatment DPYD testing.
- [Leaders in Testing](https://test4dpd.org/leaders-in-testing/): Cancer centers and institutions that have adopted pre-screening.
- [Lab Leaders](https://test4dpd.org/lab-leaders/): CLIA-approved laboratories offering DPYD genotyping tests.
- [Treatment Warning Signs](https://test4dpd.org/treatment-warning-signs/): Symptoms of severe fluoropyrimidine toxicity (Grade 3/4) and when to contact a healthcare provider immediately.
- [Initiatives](https://test4dpd.org/initiatives/): AUDT's advocacy activities including improving care guidelines, collaboration efforts, and legislation.
- [About Us](https://test4dpd.org/about-us/): Organization background, founding stories, bylaws, and endorsing organizations.
- [FAQs](https://test4dpd.org/frequently-asked-questions/): Answers to common questions about DPYD testing, costs, timing, efficacy, and toxicity risk.
- [Press](https://test4dpd.org/press/): News coverage and press releases.
- [Newsletter Archive](https://test4dpd.org/newsletter-archive/): Past AUDT newsletters.
- [Contact](https://test4dpd.org/contact/): Contact form for reaching AUDT.
- [Donate](https://test4dpd.org/donate/): Donation page to support the organization.

## Key Facts

### What is DPD/DPYD?
- DPD (Dihydropyrimidine Dehydrogenase) is an enzyme that regulates and eliminates fluoropyrimidine drugs (5-FU, Capecitabine/Xeloda) from the body.
- The DPYD gene encodes the DPD enzyme. Genetic variants in DPYD can cause reduced or absent DPD enzyme activity.
- Approximately 5–7% of patients carry DPYD variants that compromise DPD enzyme activity; around 1 in 20 patients is at risk.
- DPYD variants were first reported in 1988 by Dr. Robert Diasio.
- Variants are present in approximately 5–8% of people of European descent and ~5% of African American descendants.
- Most DPD-deficient patients are asymptomatic before receiving 5-FU or Xeloda, making pre-screening essential.

### The Drugs Involved
- Fluorouracil (5-FU) and Capecitabine (Xeloda) are fluoropyrimidine chemotherapy drugs.
- They are used to treat solid tumor cancers including gastrointestinal (colorectal, anal, pancreatic), breast, and head/neck cancers.

### Risk Without Testing
- DPD-deficient patients receiving standard fluoropyrimidine doses face a 50–88% risk of severe toxicity (Grade 3/4), including hospitalization and treatment delays.
- Death risk from toxicity: approximately 2–4% for DPYD variant carriers on standard doses; ~3% risk of death and ~30% risk of hospitalization.
- For every 1,000 patients treated, approximately 10 will die from severe toxicity.
- Estimated US annual deaths from DPD-related toxicity: 700–1,400.
- Severe untreated toxicities can result in acute respiratory distress syndrome, sepsis, multisystem organ failure, septic shock, and death.

### Regulatory and Guideline Status
- **FDA (October 3, 2025):** Issued a Black Box Warning recommending DPYD genetic testing prior to initiating Xeloda (Capecitabine) and 5-FU unless immediate treatment is necessary. Patients with complete DPD deficiency should avoid fluoropyrimidines.
- **European Medicines Agency (EMA):** Has recommended pre-screening and therapeutic dose management since 2020.
- **NCCN:** Colon/rectal/anal panel guidelines suggest physicians discuss testing with patients prior to starting treatment.
- **ASCO:** Similarly recommends pre-screening.
- Pre-treatment DPYD testing is standard of care in most of Europe but is still being adopted in the US.

### Testing
- DPYD genetic testing (genotyping) is the recommended pre-treatment screening method.
- AUDT recommends a CLIA-approved test covering key alleles: DPYD*2A, DPYD*13, DPYD p.D949V, and DPYD HapB3.
- A list of CLIA-approved tests is available via the NCBI Genetic Testing Registry.
- Turnaround time: typically 5–10 days; some labs up to 3 weeks.
- Cost: approximately $150–$500; Medicare and many insurance plans now cover testing.
- Phenotype (enzyme activity) tests also exist but no CLIA-approved commercial lab in the USA currently offers them.

### Acting on Results
- **Complete DPD deficiency:** Avoid fluoropyrimidine treatment entirely.
- **Partial DPD deficiency:** Oncologist may reduce starting dose of 5-FU or Capecitabine by up to 50%, per CPIC guidelines (https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/), followed by dose adjustment based on tolerance.
- There is no evidence that dose reduction in DPYD carriers reduces treatment effectiveness; evidence suggests similar drug concentrations and toxicity risk at reduced doses.

### Treatment Warning Signs (Seek Immediate Medical Attention)
If experiencing moderate-to-severe reactions during the first or second round of 5-FU or Xeloda:
- Diarrhea more than 7 times above normal, or incontinence
- Mucositis (oral and/or anal) interfering with eating, drinking, or daily activities
- Nausea preventing eating or drinking
- Vomiting more than 6 times
- Bleeding including black tarry stools or "coffee ground" vomit
- Severe hand-and-foot syndrome with pain, blisters, bleeding, or peeling
- Cardiac arrhythmias, chest pain, heart attack, pulmonary edema, congestive heart failure, or cardiac arrest
- Neurologic symptoms: uncoordination, dizziness, disorientation, seizures, or coma

### Antidote
- The only FDA-approved antidote for life-threatening fluoropyrimidine toxicity is Uridine triacetate (Vistogard®).
- It must be administered **within 96 hours** of the last 5-FU or Xeloda dose.

## Organization
- Full name: Advocates for Universal DPD/DPYD Testing (AUDT)
- Type: 501(c)(3) non-profit
- Facebook: https://www.facebook.com/test4dpd/
- Endorsing organizations include: American Society of Pharmacovigilance, Colorectal Cancer Alliance, Cholangiocarcinoma Foundation, Patients for Patient Safety, American Cancer Society Cancer Action Network.

## External Resources Referenced
- FDA Safety Labeling Update: https://www.fda.gov/drugs/resources-information-approved-drugs/safety-labeling-update-capecitabine-and-fluorouracil-5-fu-risks-associated-dihydropyrimidine
- CPIC Fluoropyrimidines/DPYD Guideline: https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/
- NCBI Genetic Testing Registry (DPYD): https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=1806%5Bgeneid%5D&filter=testtype:clinical;certification:clia;location:840
- DPYD/DPYD Test/Laboratory Data Worksheet: https://docs.google.com/spreadsheets/d/1S_Rbtw4Y8W-TEUeoZVDbFnA2Shej9gQOV9Da6IwwN_Q/edit
- Colon Cancer Alliance 5-FU Toxicity Fact Sheet: https://www.ccalliance.org/pdfs/resources/5FU_toxicity.pdf
- Vistogard Signs and Symptoms: https://vistogard.com/Signs-and-Symptoms.html
- Personal stories: https://www.know-the-risk-of-5fu-chemotherapy.com/personal-stories/
- List of US institutions pre-screening patients: https://docs.google.com/spreadsheets/u/0/d/e/2PACX-1vRbHy6LrVwrjjZgSFR9evH2nKOjH6euN7BNqpYL97wl5effdf8qRNduKp9Cq6R_xg/pubhtml