Implementing DPYD*2A Genotyping in Clinical Practice: The Quebec, Canada, Experience

• DOI: 10.1002/onco.13626
• Publication Date: 2020-12-04T12:33:18Z
• Authors: Catherine Jolivet; Rami Nassabein; Denis Soulières; Xiaoduan Weng; Carl Amireault; Jean-Pierre Ayoub; Patrice Beauregard; Normand Blais; Christian Carrier; Alexis-Simon Clou...; Alexandra Desnoyers; Anne-Sophie Lemay; Frédéric Lemay; Rasmy Loungnarath; Jacques Jolivet; François Letendre; Mustapha Tehfé; Charles Vadnais; Daniel Viens; Francine Aubin
• Keywords: DPYD; Mucositis; Dihydropyrimidine dehydrogenase

Abstract Background Fluoropyrimidines are used in chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. DPYD*2A polymorphism is one of the most studied variants. The study objective was document impact implementing this test routine clinical practice. Methods We retrospectively performed chart reviews all patients who tested positive a heterozygous or homozygous mutation samples obtained from throughout province Quebec, Canada. Results During period 17 months, 2,617 were tested: 25 positive. All White. Twenty-four (0.92%), and (0.038%). Data available 20 patients: 15 upfront, whereas five identified after Of confirmed toxicities, had grade 4 cytopenias, 80% ≥3 mucositis, 20% 3 rash, diarrhea. Eight with prior treatment received fluoropyrimidine-based at reduced initial doses. average fluoropyrimidine dose intensity during 50%. No toxicities observed. results an 6 days, causing no significant delays initiation. Conclusion Upfront genotyping before feasible practice prevent hospitalizations without delaying administration doses appears be safe DPYD*2A. Implications Practice part This retrospective analysis demonstrates that upfront DPYD approach reported previously, but insufficient data concerning its application real available. likely first experience systematic over Canada North America as well.