mutation that results in defective DPD protein. Nineteen molecular defects in the DPYD gene have been studied but not all mutations affect DPD enzyme activity.4 Lethal consequences have been reported… Click to show full abstract
mutation that results in defective DPD protein. Nineteen molecular defects in the DPYD gene have been studied but not all mutations affect DPD enzyme activity.4 Lethal consequences have been reported in heterozygous DPYD*2A mutation carriers and homozygous DPYD*2A mutations due to severe 5-FU-induced toxicity.4 New pharmacogenomics approaches have been launched to identify relevant inherited variations to better predict patient responses to 5-FU.4 It is hence prudent that we learn and understand more to first predict and then prevent toxicities secondary to 5-FU/Xeloda. There has been no consensus yet on screening of DPYD mutations before treatment. Multiple DPYD allele variants have been identified, but the degree of toxicity has been inconsistent among genetic variants, as some of these individuals have toxicity profiles similar to those of the general population. Whenever the patient has unexplained neutropenia and Grade III & IV gastrointestinal toxicity with a standard dose of 5-FU/Xeloda, we should consider investigating the DPYD mutation analysis. If a patient is determined to be positive for DPD deficiency, dose modification and/or accepted alternative treatments should be discussed with the patient.
               
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