Genotype-Guided Dose of Fluoropyrimidine May Decrease Toxicity
Using a genotype-guided dose of fluoropyrimidine in DPYD*2A variant allele carriers significantly reduced grade 3 or higher toxicities.
Using a genotype-guided dose of fluoropyrimidine in DPYD*2A variant allele carriers significantly reduced grade 3 or higher toxicities compared to historical controls (73% vs 28%; P < .001).1
Fluoropyrimidines are frequently used in the treatment of patients with cancer, however it is well established that a polymorphism in the fluoropyrimidine metabolizing enzyme dihydropyrimidine dehydrogenase (DPD) is associated with severe and sometimes life-threatening toxicity.
In a recent study published in the Journal of Clinical Oncology researchers sought to determine the benefit of DPYD*2A genotype-guided dosing, analyzing factors such as feasibility, safety, and cost. The researchers screened 2038 patients for DPYD*2A and found that 1.1% (22 patients) were heterozygous polymorphic.
Patients with DPYD*2A variant alleles were subsequently treated with a median fluoropyrimidine dose intensity of 48% (range: 17%-91%).
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In addition to finding a reduction in grade 3 or higher toxicities, researchers also found a reduction in drug induced death (10% vs 0%) and a reduction in the average total treatment cost per patient ($3,767 per screened patient vs $3,828 per unscreened patient).
“DPYD*2A genotype–guided dosing results in adequate systemic drug exposure and significantly improves safety of fluoropyrimidine therapy for the individual patient,” concluded researchers.
- Deenen MJ, Meulendijks D, Cats A, et al. Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis [online ahead of print November 16, 2015]. J Clin Oncol. doi: 10.1200/JCO.2015.63.1325.