To prospectively evaluate the efficacy and safety of DPYD-guided dosing strategies in a real-world clinical setting, specifically by comparing the incidence of severe (Grade 3 and 4) fluoropyrimidine-related toxicities of heterozygous DPYD variant patients assigned to DPYD-guided reduced dosing versus patients with standard dosing in the control arm.
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.
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.
Patients for whom 5-FU or Capecitabine therapy is contraindicated or not deemed appropriate in the judgment of the treating physician.
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
Parallel
Fluorouracil injection
DrugExperimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
Xeloda
DrugExperimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
incidence of severe fluoropyrimidine-related toxicities (Grade 3-5)
Number and proportion of patients experiencing Grade 3, 4, or 5 toxicities related to 5-FU or Capecitabine, as defined by CTCAE v5.0.
Patterns of Dose Modification (Reductions and Escalations)
Number and type of dose modifications (reductions, escalations, discontinuations) in each arm,
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