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

The oncologist

article

Catherine Jolivet¹  Alexis-Simon Cloutier²  Alexandra Desnoyers³  Anne-Sophie Lemay⁴  Frédéric Lemay³  Rasmy Loungnarath¹  Jacques Jolivet⁵  François Letendre⁶  Mustapha Tehfé¹  Charles Vadnais¹  Daniel Viens⁷  Rami Nassabein¹  Francine Aubin¹  Denis Soulières¹  Xiaoduan Weng¹  Carl Amireault²  Jean-Pierre Ayoub¹  Patrice Beauregard³  Normand Blais¹  Christian Carrier⁴ 

[1] Centre Hospitalier de l'Université de Montréal (CHUM);Hôpital Pierre-Boucher;Centre Hospitalier de l'Université Sherbrooke;Centre Hospitalier Régional Trois-Rivières;Centre Intégré de Santé et de Services Sociaux (CISSS) des Laurentides;CISSS Montérégie Ouest;Hôpital Sainte-Croix

关键词: Fluoropyrimidines toxicity;    DPYD genotyping;    DPYD*2A;    Fluorouracil;    Capecitabine;   

DOI  :  10.1002/onco.13626

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

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

【 授权许可】

CC BY|CC BY-NC