Evidence to Support Testing

Two medical professionals discuss the Pros and Cons of universal DPYD pre-screening. Dr. Dan Hertz, PharmD at the University of Michigan presents the benefits of testing while Dr. Suneel D. Kamath, MD at the Cleveland Clinic discusses the challenges with clinical implementation of DPYD testing. Recording date is January 2022.

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Medical Journal Articles

DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis

(2018) concludes:

  • Prospective screening is feasible in clinical practice
  • Genotype guided dose reduction treatments improved patient safety
  • Genotype guided individual dosing should become the new standard of care
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DPYD variants as predictors of 5-fluorouracil toxicity in adjuvant colon cancer treatment (NCCTG N0147)

(2014) found:

  • “In the largest study to date, (2594 patients with adverse event – AE – data), statistically significant associations were found between DPYD variants (DPYD*2A and D949V) and increased incidence of grade 3 or greater 5FU-AEs in patients treated with adjuvant 5-FU-based combination chemotherapy.”
  • Patients with DPYD variant associated with deficiency suffered severe toxicity between 50-88% of the time when treated with standard dosing
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Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis

(2016) found:

  • Genotype guided dosing for this single, and most common variant, resulted in lower rates of severe toxicity (from 73 % to 48%) and deaths from 10% to 0%
  • “DPYD*2A genotype–guided dosing results in adequate systemic drug exposure and significantly improves safety of fluoropyrimidine therapy
    for the individual patient.”
  • Average total treatment cost was lower for screening than treatment without screening.
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Pathogenic DPYD variants and treatment‐related mortality in patients receiving fluoropyrimidine chemotherapy: A systematic review and meta‐analysis

(2021) concluded:

“Patients with pathogenic DPYD gene variants who receive standard-dose fluoropyrimidine chemotherapy have greatly increased risk for treatment-related death.”

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Videos

Dr. Julien Taieb-Hegp’s presentation entitled: “Should DPD Deficiency Be Searched (sic) Before Starting 5FU?” at the World Gastrointestinal Conference of the European Society of Medical Oncologists in 2020.