DPYD Pharmacogenomics and Fluoropyrimidine (FP) Dose-Adjustment
Rutgers, The State University of New Jersey
Summary
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.
Description
Fluropyrimidines (FPs), such as 5-Fluorouracil (5-FU) and Capecitabine, are cornerstone chemotherapy agents widely used in the treatment of various cancers, including gastrointestinal, head and neck, and breast cancers. Dosing of FP, specifically 5-FU, has been a challenge since this drug was first synthesized in 1957 by Charles Heidelberger1. 5FU had been given on numerous schedules and doses, including weekly 24 hr infusion, 48-hour infusion every two weeks, and daily five-times-a-day infusion with leucovorin (Mayo Regimen) and weekly bolus with leucovorin infusion (Roswell, Park Regimen). I…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 norma…
Interventions
- DrugFluorouracil injection
Experimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
- DrugXeloda
Experimental arm Fluorouracil injection with possible escalation to 75 or 100 percent if tolerated.
Locations (12)
- RWJBarnabas Health Clara Maas Medical CenterBelleville, New Jersey
- Trinitas Hospital and Comprehensive Cancer CenterElizabeth, New Jersey
- RWJBarnabas Health - Robert Wood Johnson University Hospital, HamiltonHamilton, New Jersey
- RWJBarnabas Health Jersey City Medical CenterJersey City, New Jersey
- Cooperman Barnabas Medical CenterLivingston, New Jersey
- Jack and Sheryl Morris Cancer CenterNew Brunswick, New Jersey