Optimizing fluoropyrimidine therapy through dihydropyrimidine dehydrogenase polymorphism testing.

Fluoropyrimidines (FP), including 5-fluorouracil and its prodrug capecitabine, are commonly employed in treating various solid tumors. Nonetheless, their use is frequently constrained by severe toxicities in 20%-30% of patients. Pharmacogenetic testing for dihydropyrimidine dehydrogenase (DPYD) deficiency, based on DPYD polymorphisms, has notably decreased severe adverse events, improving the safety of FP therapy. A recent D'Amato study evaluated the prevalence of DPYD polymorphisms and their effect on FP tolerability among Italian patients with gastrointestinal cancers. Although this study provided important insights into the significance of DPYD testing, its retrospective nature, inconsistency in testing DPYD variants, and lack of consideration for socioeconomic and confounding factors showed considerable limitations. Expanding the screening to include DPYD variants, addressing confounding biases through robust statistical analyses, and implementing prospective studies are critical next steps to strengthen the clinical evidence. Furthermore, the absence of a comprehensive cost-effectiveness analysis highlights the need for further financial assessments to advocate for broader implementation. We emphasized integrating DPYD-guided dosing, pre-treatment genetic counseling, and standardized testing procedures into clinical practice to improve patient outcomes and minimize treatment-related toxicities.