Impact of pharmacist-driven DPYD genotype-guided dosing for fluoropyrimidine-based chemotherapy regimens.

451 Background: Variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase (DPD), are associated with impaired metabolism of fluoropyrimidines including fluorouracil (5-FU) and its oral prodrug, capecitabine. Patients with these variants are at increased risk for severe and potentially life-threatening toxicities. In December 2022, Dana-Farber Cancer Institute (DFCI) implemented a standardized, institution-wide program to support preemptive DPYD genotyping and genotype-guided dosing for patients initiating fluoropyrimidine-based therapy. The initiative included automated electronic health record prompts, pharmacist-led genotype-based dosing recommendations, as well as provider, pharmacist, nurse, and patient education. Methods: In September 2024, a new pharmacist-driven workflow was launched to enhance re-escalation rates in patients undergoing dose reduction based on DPYD genotyping and to operationalize genotype-guided dose initiation and adjustment in the outpatient setting. The workflow includes systematic identification of patients without prior exposure to 5-fluorouracil (5-FU) or capecitabine, automated prompts for DPYD testing, and a closed-loop notification system for abnormal results. Pharmacists provide dose modification and re-escalation recommendations based on standardized guidelines. The process also includes structured documentation and tracking of genotyping results and corresponding dose recommendations. Targeted training was delivered to clinical staff to ensure consistent adoption and adherence to the workflow. Results: Following the implementation of the pharmacist-driven DPYD workflow, DPYD gene deficiencies were identified in 28 patients receiving 5-fluorouracil and 17 patients receiving capecitabine out of the 810 patients that were tested from September 2024 to May 2025. Pharmacist-led genotype-guided dose reduction recommendations were provided for all identified patients, with 40/45 recommendations accepted by oncologist. Among these,14 patients were dose re-escalated based on clinical tolerability and in accordance with the standardized dosing recommendations. Conclusions: The implementation of a pharmacist-driven workflow for DPYD genotype interpretation and dose recommendations is both feasible and impactful in the outpatient oncology setting. This proactive approach supports personalized chemotherapy dosing, potentially reducing both the risk of over- and undertreatment.