A recent article [PMID: 26573078] and editorial [PMID: 26644533] in The Journal of Clinical Oncology looked at prospective testing for DPYD *2A and prevention of grade 3 or higher toxicity. The study examined a large number of patients (n=2,038) and identified 22 carriers of DPYD *2A who then received a reduced dose of fluoropyrimidines or alternative drug regimen, as per CPIC and DPWG guidelines. The FDA and EMA drug labels for fluorouricil and capecitabine do not currently recommend DPYD testing prior to fluoropyrimidine therapy.
Deenen et al stated that “the risk of grade ≥ 3 toxicity was thereby significantly reduced from 73% (95% CI, 58% to 85%) in historical controls (n = 48) to 28% (95% CI, 10% to 53%) by genotype-guided dosing (P <0.001); drug-induced death was reduced from 10% to 0%.”
The authors found when average total treatment costs were examined, “the cost per patient was lower for screening (€2,772 [$3,767]) than for nonscreening (€2,817 [$3,828]), outweighing screening costs. “
Although several DPYD variants have been reported to decrease DPD activity the frequency of each are very low, (in the range of 1%, see supplementary table 3 from the CPIC guideline) which has been considered a barrier to testing. As the editorial states “The per-genotype cost of genotypic tests is continually decreasing, and studies of pre-emptive genotyping have suggested that large-scale, multitarget tests could further drive down that cost in the future”
A follow up study from the same authors is already underway and will look at DPYD*2A, rs67376798, rs56038477/HapB3 and DPYD*13.
The full dosing guidelines, including details for all functional variants of DPYD, and drug labels regarding DPYD and fluoropyrimidines can be found on PharmGKB.