A Pharmacogenomic Basis for Tolerance of 5-Fluorouracil Following Early, Severe Toxicity from Capecitabine in a CDA Ultrarapid Metabolizer Colon Cancer Patient: A Case Report

作者：Tinashe Mazhindu, Zedias Chikwambi, Edith Matsikidze, Kevin Grimes, Margaret Borok, Ntokozo Ndlovu, Collen Masimirembwa · 发表于：Cancer Management and Research · 年份：2026 · DOI：10.2147/cmar.s571794 · 被引用次数：2 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Treatment and Pharmacology、Genetic factors in colorectal cancer

Introduction: Capecitabine is an oral prodrug that is converted to 5-FU via three enzyme-catalysed steps: carboxylesterase (CES), cytidine deaminase (CDA), and thymidine phosphorylase (TYMS). Approximately 80-90% of 5-FU, whether from capecitabine or direct administration, is quickly inactivated by dihydropyrimidine dehydrogenase (DPD), encoded by DPYD. Preemptive testing for four pathogenic DPYD variants that reduce DPD activity is advised; however, currently, no evidence for CES, CDA, or TYMS has necessitated a similar recommendation despite polymorphisms in these genes potentially causing treatment toxicity. The current preemptive testing guidelines for 5-FU and capecitabine are similar. Case Presentation: was prescribed adjuvant oxaliplatin and capecitabine post-hemicolectomy. On day 16 of the first cycle, she presented with severe gastrointestinal, myelosuppressive, hand and foot side effects and enterocolitis infection. She underwent a pharmacogenomic workup with whole-exome sequencing and was noted to be genetically DPD non-deficient (DPYD *1/*9A). She was found to express CDA rs3215400 (c.-33delC) and CDA rs1048977, both of which are associated with an increased risk of toxicity from capecitabine. CDA rs3215400 has been specifically described as an ultrametabolizer variant with an observation to increase enzyme activity by 3-7 fold and the occurrence of adverse drug events in capecitabine. After recovery and follow-up, she continued to receive 5-FU, leucovorin, and ox...