Krishnan A. Optimizing fluoropyrimidine therapy through dihydropyrimidine dehydrogenase polymorphism testing. World J Gastrointest Oncol 2025; 17(5): 101320 [DOI: 10.4251/wjgo.v17.i5.101320]
Corresponding Author of This Article
Arunkumar Krishnan, MD, MS, Assistant Professor, Research Scientist, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. May 15, 2025; 17(5): 101320 Published online May 15, 2025. doi: 10.4251/wjgo.v17.i5.101320
Optimizing fluoropyrimidine therapy through dihydropyrimidine dehydrogenase polymorphism testing
Arunkumar Krishnan
Arunkumar Krishnan, Department of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC 28204, United States
Author contributions: Krishnan A contributed to the concept of the study, drafted the manuscript, and performed the review and editing. The manuscript was critically revised for important intellectual content and finalized by Krishnan A.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arunkumar Krishnan, MD, MS, Assistant Professor, Research Scientist, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Received: September 10, 2024 Revised: January 22, 2025 Accepted: February 10, 2025 Published online: May 15, 2025 Processing time: 246 Days and 8.2 Hours
Abstract
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 et al 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.
Core Tip: Dihydropyrimidine dehydrogenase (DPYD) polymorphism testing is important for minimizing severe fluoropyrimidine (FP)-related toxicities in cancer patients. This pharmacogenetic strategy promotes personalized dosing, improving patient safety and tolerability. A study by D’Amato et al assessed the prevalence of DPYD polymorphisms and their impact on FP tolerability in patients with gastrointestinal malignancies. However, it is important to tackle study limitations such as retrospective designs, variability in testing, and confounding factors and assess the cost-effectiveness of including DPYD testing in standard clinical practice. Future studies should broaden genetic screening, provide pre-treatment counseling, and establish standardized methodologies to improve clinical relevance.
