Medical Journal Articles
DPYD Testing: A Guide for Oncologists for Discussing with Patients.
“All You Need to Know About DPYD Testing for Patients Treated with Fluorouracil and Capecitabine: A Practitioner-Friendly Guide” (2020).
This paper provides “a single guide for health care professionals to make an evidence-based decision about DPYD testing for patients with cancer” … and “the essential knowledge base for oncologists to have an informed discussion with their patients about the genetic testing for DPYD. This document assists practitioners in quickly evaluating whether, when, where, and how to order a DPYD genetic test”.
Benefits of DPYD Testing
“Assessment of the Clinical Utility of Pretreatment DPYD Testing for Patients Receiving Fluoropyrimidine Chemotherapy”, 2022.
This paper addresses the NCCN’s concern with the efficacy of reduced dosing for DPD deficient patients and finds “no direct evidence of efficacy reduction”.
“DPYD Testing: Time to Put Patient Safety First”, 2023.
“We recommend that pretreatment DPYD variant testing should be incorporated immediately into the standard of care for fluoropyrimidine regimens. Since fluoropyrimidine pharmacokinetic exposure is higher in reduced-function DPYD variant carriers, starting at a reduced dose and titrating upward to avoid undue toxicity should be adequate to maximize benefit while reducing risk in patients carrying heterozygous genotypes.”
Prospective Trials of DPYD Testing
Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis, 2016.
- 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.
DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis, 2018.
- 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
Dangers of Typical Dosing in DPYD Carriers
Pathogenic DPYD variants and treatment‐related mortality in patients receiving fluoropyrimidine chemotherapy: A systematic review and meta‐analysis, 2021.
“Patients with pathogenic DPYD gene variants who receive standard-dose fluoropyrimidine chemotherapy have greatly increased risk for treatment-related death.”
Clinical Relevance of DPYD Variants… as Predictors of Severe Fluoropyrimidine-hToxicity: A Systematic Review and Meta-Analysis of Individual Patient Data.
This 2015 Meulindijks study found: “Clinical validity has now been established for four DPYD variants… and upfront screening for these mutations with dose adaptation in variant allele carriers is advised to improve patient safety…”
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.