Real-World Impact of an In-House Dihydropyrimidine Dehydrogenase ( DPYD ) Genotype Test on Fluoropyrimidine Dosing, Toxicities, and Hospitalizations at a Multisite Cancer Center

作者：D. Grace Nguyen, Sarah Morris, Alicia Hamilton, Simeon Owuor Kwange, Nury Steuerwald, James T. Symanowski, Donald C. Moore, Sarah Hanson, Kaitlyn Mroz, Karine Lopes, Chris Larck, Laura W. Musselwhite, Kunal C. Kadakia, Brinda Koya, Seungjean Chai, Kwabena Osei-Boateng, Sini Kalapurakal, Kristen Swift, Jimmy J. Hwang, Jai N. Patel · 发表于：JCO Precision Oncology · 年份：2024 · DOI：10.1200/po.23.00623 · 被引用次数：16 · 研究领域：Colorectal Cancer Treatments and Studies、Acute Lymphoblastic Leukemia research、Carcinogens and Genotoxicity Assessment

PURPOSE Fluoropyrimidine-related toxicity and mortality risk increases significantly in patients carrying certain DPYD genetic variants with standard dosing. We implemented DPYD genotyping at a multisite cancer center and evaluated its impact on dosing, toxicity, and hospitalization. METHODS In this prospective observational study, patients receiving (reactive) or planning to receive (pretreatment) fluoropyrimidine-based chemotherapy were genotyped for five DPYD variants as standard practice per provider discretion. The primary end point was the proportion of variant carriers receiving fluoropyrimidine modifications. Secondary end points included mean relative dose intensity, fluoropyrimidine-related grade 3+ toxicities, and hospitalizations. Fisher's exact test compared toxicity and hospitalization rates between pretreatment carriers, reactive carriers, and wild-type patients. Univariable and multivariable logistic regression identified factors associated with toxicity and hospitalization risk. Kaplan-Meier methods estimated time to event of first grade 3+ toxicity and hospitalization. RESULTS Of the 757 patients who received DPYD genotyping (median age 63, 54% male, 74% White, 19% Black, 88% GI malignancy), 45 (5.9%) were heterozygous carriers. Fluoropyrimidine was modified in 93% of carriers who started treatment. In 442 patients with 3-month follow-up, 64%, 31%, and 30% of reactive carriers, pretreatment carriers, and wild-type patients had grade 3+ toxicity, respectively...