DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment

Prior treatment

• Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician.

Other

• Patients with two DPYD variants (homozygous deletions or non-functional genetic variants, or double heterozygotes with two different abnormalities) should not receive 5-FU or Capecitabine and are therefore excluded from the study.
• Pregnant Women and Children

• Diagnosis of cancer in either the adjuvant or metastatic setting requiring initial therapy with 5-FU or Capecitabine.
• DPYD testing performed by a CLIA-certified laboratory (i.e., Guardant 360 or Caris blood testing for genomic profiling, DPYD testing by the Mayo Clinic or other certified laboratory) with results available before starting chemotherapy.
• DPYD testing results falling into one of the following cohorts for first-line therapy with a fluoropyridine:
• Study Cohort: Patients with one DPYD variant in one gene (heterozygotes).
• Control Arm: Patients with normal or wild-type DPYD genes, for comparison, will be treated at the usual 100% dose.
  • --FOLFOX regimen (N=50)
• ECOG Performance Status 0-2.
• Measurable disease or non-measurable disease allowed, including adjuvant 5-FU-based regimens.