New Publication: DPYD Testing: Time to Put Patient Safety First

Posted in Cancer Cell Biology Program News

New Publication by Sandra Swain, et al.

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. Homozygous patients are at unacceptably high risk of fatal toxicity, and fluoropyrimidine therapy should be avoided unless it is absolutely necessary, in which case < 25% of the dose should be administered with DPD phenotyping tests and therapeutic drug monitoring. These methods are already recommended in the CPIC guidelines, and high evidence variants are included therein.10 Thus, we recommend oncologists order testing before initiating fluoropyrimidine chemotherapy and follow the CPIC dosing guidelines, and the FDA should require updates to the package insert. We recommend that NCCN and ASCO treatment guidelines be modified to reflect the relationship between fluoropyrimidine and toxicity and that a priori testing should be adopted as the standard of care.