Genotype-Guided Dose of Fluoropyrimidine May Decrease Toxicity

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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.

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.

Reference

  1. 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.

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%). 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.

 

Reference

1.     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

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