Considerations for the clinical implementation of DPYD and UGT1A1-guided chemotherapy.

Abstract

Existing literature demonstrates the benefits of DPYD and UGT1A1 pharmacogenetic (PGx) testing to reduce toxicity from fluoropyrimidines and irinotecan, respectively. The Food and Drug Administration (FDA) has provided UGT1A1-guided irinotecan dosing for 20 years, and in 2025, the FDA and National Comprehensive Cancer Network both updated their guidance to recommend DPYD testing prior to fluoropyrimidine therapy. As such, there is an increasing interest in testing and a need for guidance describing implementation strategies. This review summarizes conclusions from DPYD and/or UGT1A1 implementation initiatives and describes key takeaways related to perspectives, workflow, cost, and supportive care from 32 included articles. Perspectives toward testing were generally positive, although barriers such as turnaround time and cost concerns were still identified. Workflow integration varied by institution, but a clear delineation of duties was consistently necessary. For both DPYD and UGT1A1, real-world studies and modeling data indicate testing is cost-effective. PGx testing was underutilized for supportive care medications despite its relevance, but there is an opportunity to leverage panel-based approaches to increase utilization without additional workflow burden. Description of these key considerations and takeaways reported by those implementing DPYD and/or UGT1A1 PGx testing would be beneficial to institutions in the early phases of implementation.