Clinical validity of a DPYD‐based pharmacogenetic test to predict severe toxicity to fluoropyrimidines. Issue 12 (14th July 2015)

• Record Type: Journal Article
• Authors: Toffoli, Giuseppe; Giodini, Luciana; Buonadonna, Angela; Berretta, Massimiliano; De Paoli, Antonino; Scalone, Simona; Miolo, Gianmaria; Mini, Enrico; Nobili, Stefania; Lonardi, Sara; Pella, Nicoletta; Lo Re, Giovanni; Montico, Marcella; Roncato, Rossana; Dreussi, Eva; Gagno, Sara; Cecchin, Erika
• Is Part Of: International journal of cancer. Volume 137:Issue 12(2015:Dec. 15)
• Page Start: 2971
• Page End: 2980
• Publication Date: 2015-07-14
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29654
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Pre‐therapeutic <italic>DPYD</italic> pharmacogenetic test to prevent fluoropyrimidines (FL)‐related toxicities is not yet common practice in medical oncology. We aimed at investigating the clinical validity of <italic>DPYD</italic> genetic analysis in a large series of oncological patients. Six hundred three cancer patients, treated with FL, have been retrospectively tested for eight <italic>DPYD</italic> polymorphisms (<italic>DPYD</italic>‐rs3918290, <italic>DPYD</italic>‐rs55886062, <italic>DPYD</italic>‐rs67376798, <italic>DPYD</italic>‐rs2297595, <italic>DPYD</italic>‐rs1801160, <italic>DPYD</italic>‐rs1801158, <italic>DPYD</italic>‐rs1801159, <italic>DPYD</italic>‐rs17376848) for association with Grade ≥3 toxicity, developed within the first three cycles of therapy. <italic>DPYD</italic>‐rs3918290 and <italic>DPYD</italic>‐rs67376798 were associated to Grade ≥3 toxicity after bootstrap validation and Bonferroni correction (<italic>p</italic> = 0.003, <italic>p</italic> = 0.048). <italic>DPYD‐</italic>rs55886062 was not significant likely due to its low allelic frequency, nonetheless one out of two heterozygous patients (compound heterozygous with <italic>DPYD</italic>‐rs3918290) died from toxicity after one cycle. Test specificity for the analysis of <italic>DPYD</italic>‐rs3918290, <italic>DPYD‐</italic>rs55886062 and <italic>DPYD</italic>‐rs67376798 was assessed to 99%. Among the seven patients carrying one variant <italic>DPYD</italic>‐rs3918290, <italic>DPYD‐</italic>rs55886062 or <italic>DPYD</italic>‐rs67376798 allele, not developing Grade ≥3 toxicity, 57% needed a FL dose or schedule modification for moderate chronic toxicity. No other <italic>DPYD</italic> polymorphism was associated with Grade ≥3 toxicity. Our data demonstrate the clinical validity and specificity of the <italic>DPYD</italic>‐rs3918290, <italic>DPYD‐</italic>rs55886062, <italic>DPYD</italic>‐rs67376798 genotyping test to prevent FL‐related Grade ≥3 toxicity and to preserve treatment compliance, and support its introduction in the clinical practice.</p> </abstract>