<i>DPYD</i> Testing: Time to Put Patient Safety First
Sharyn D. Baker, Susan E. Bates, Gabriel A. Brooks, William L. Dahut, Robert B. Diasio, Wafik S. El‐Deiry, William E. Evans, William D. Figg, Daniel L. Hertz, J. Kevin Hicks, Suneel Kamath, Pashtoon Murtaza Kasi, Todd C. Knepper, Howard L. McLeod, Peter H. O’Donnell, Mary V. Relling, Michelle A. Rudek, Tristan M. Sissung, D. Max Smith, Alex Sparreboom, Sandra M. Swain, Christine M. Walko
Abstract
In 2018, a patient received capecitabine without prior testing for dihydropyrimidine dehydrogenase (DPYD) and later presented with vomiting, rash, and diarrhea.The hospital failed to provide uridine triacetate in a timely fashion, and the patient died.The patient's widow filed a wrongful death lawsuit against Oregon Health Sciences University (OHSU) and assisted in the formation of a nonprofit organization to advocate for DPYD testing for fluoropyrimidines.A settlement for $1 million US dollars was reached requiring OHSU oncologists to undergo education about DPYD testing and inform their patients about its availability. 1Clinical practice guidelines from the National Comprehensive Cancer Network (NCCN) and ASCO still do not support testing for DPYD genetic variants before fluoropyrimidine chemotherapy.The US Food and Drug Administration (FDA) package inserts for capecitabine and fluorouracil (FU) acknowledge patients with dihydropyrimidine dehydrogenase protein (DPD) deficiency have increased risk of life-threatening toxicity; however, instead of recommending preemptive testing, they posit an unlikely scenario in which patients who have known DPD deficiency should discuss it with their physicians. 2,3The European Medicines Agency, the French National Agency for the Safety of Medicines and Health Products, and the Medicines and Healthcare products Regulatory Agency have each approved guidelines for preemptive DPYD testing for patients treated with fluoropyrimidines.