DPYD Genotype-guided Dose Optimization of 5-Fluorouracil in Individuals with Pancreatic Cancer

Systemic fluoropyrimidines (FP) including intravenous 5-fluorouracil (IV 5-FU) and its oral prodrug capecitabine are used to treat a variety of solid tumors such as pancreatic, colorectal, and breast cancer. National Comprehensive Cancer Network (NCCN) guidelines recommend FOLFIRINOX (IV 5-FU + leucovorin + irinotecan + oxaliplatin) or modified FOLFIRINOX (mFOLFIRINOX) as a preferred first-line treatment for all stages of pancreatic cancer. NALIRI (IV-FU, leucovorin and liposomal irinotecan) regimen is often considered as subsequent-line therapy for those who did not receive FOLFIRINOX as initial therapy. In addition, capecitabine is used in combination with gemcitabine as adjuvant treatment. Often, capecitabine is also used as a radiosensitizer for those considered candidates for radiation. Common toxicities of systemic fluoropyrimidines include fatigue, neutropenia, diarrhea, and vomiting. This expert review highlights the effects of genetic variants in the DPYD gene and provides recommendations for adjusting 5-FU dose based on pharmacogenetics.