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…