DPYD and Capecitabine, Fluorouracil

Normal Metabolizer

Clinical Implication

  • Normal DPD enzyme activity.
  • Normal response expected.

Therapeutic Recommendation

  • Use standard dose of fluoropyrimidines.

Intermediate Metabolizer with an enzyme Activity Score of 1.5

Clinical Implication

  • Decreased DPD enzyme activity.
  • Increased risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).

Therapeutic Recommendation

  • Reduce starting dose by 50%, thereafter titrate dose based on toxicity tolerance or therapeutic drug monitoring.

Intermediate Metabolizer with an enzyme Activity Score of 1

Clinical Implication

  • Decreased DPD enzyme activity.
  • Increased risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).

Therapeutic Recommendation

  • Reduce starting dose by 25 to 50%, thereafter titrate dose based on toxicity tolerance or therapeutic drug monitoring.

Poor Metabolizer with an enzyme Activity Score of 0.5

Clinical Implication

  • Little to no DPD enzyme activity.
  • Very high risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).

Therapeutic Recommendation

  • Avoid fluoropyrimidines and use alternative agent. If alternatives are not appropriate and phenotype testing is unavailable to estimate starting dose, may consider an initial dose reduction of 75% and utilize therapeutic drug monitoring.

Poor Metabolizer with an enzyme Activity Score of 0

Clinical Implication

  • Little to no DPD enzyme activity. 
  • Very high risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).

Therapeutic Recommendation

  • Avoid fluoropyrimidines and use alternative agent.

Unable to Genotype or Assay Failure

  • The analysis failed to yield an informative result and thus no genotype is reported.

Reference

  • Amstutz U et al. Clin Pharmacol Ther. 2018 Feb;103(2):210-216. PMID: 29152729.

Resources