ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1645188
This article is part of the Research TopicGenetic and Pharmacological Frontiers in Cancer TreatmentView all 6 articles
DPYD-Guided Fluoropyrimidine Dose Adjustment in Colorectal Cancer DPYD Carriers: Start Slower to Finish Stronger
Provisionally accepted- 1Instituto de Investigacion Hospital Universitario La Paz, Madrid, Spain
- 2Hospital Universitario La Paz, Madrid, Spain
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Fluoropyrimidines (FP) are the mainstay of colorectal cancer (CRC) treatment, but can cause severe toxicity in up to 40% of patients. Variants in the DPYD gene are associated with these adverse events. A DPYD-guide dose adjustment is now recommended in Europe. This ambispective study aims to analyze the FP-related severe toxicity and the FP dose adjustment in heterozygous DPYD variant carriers with colorectal cancer, comparing a DPYD-guided FP dose adjustment (DA) approach to the non-DPYD-guided FP dose adjustment (NDA). 1.279 DPYD genotyping reports were issued. Sixty patients were identified with DPYD variants. Twenty-five CRC patients (17 in the DA cohort and 8 in the NDA cohort) were included in the analysis. Thirty-five patients were excluded from the analysis because they did not satisfy any of the study's inclusion criteria. Reasons for exclusion included having a diagnosis other than colorectal cancer, not receiving fluoropyrimidine treatment, participation in a clinical trial, or insufficient follow-up. Of the twenty-five patients included, sixteen patients (94%) started with a 50% FP dose reduction in the DA cohort while 7 out of 8 patients (87%) in the NDA cohort received 100% of dose in cycle 1. In the DA cohort, 12% of patients experienced severe fluoropyrimidines-related adverse events, compared to 50% in the NDA cohort (OR=0.13; 95%CI: 0.01-0.93; p=0.05). FP discontinuation due to severe toxicity occurred in 6% of patients in the DA cohort versus 50% in the NDA cohort (OR=0.06; 95%CI: 0.003-0.55, p=0.02). These findings suggest that DPYD-guided dose adjustment significantly reduces both the incidence of severe toxicity and the rate of treatment discontinuation in CRC patients. Initiating treatment with a 50% FP reduction allows for dose escalation in patients who exhibit good tolerance and avoid the discontinuation for those patients intolerant to higher doses thereby improving overall treatment adherence and completion.
Keywords: Fluoropyrimidines, DPYD, colorectal cancer, Toxicity, discontinuation
Received: 11 Jun 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Rosas-Alonso, Salas, Perez Wert, Hoyo, Martín-López, Martínez-Pérez, Ruiz-Gutiérrez, Jiménez-Bou, Peña, Arias, Custodio, Losantos-García, Borobia, Feliu and Ghanem. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Rocio Rosas-Alonso, Instituto de Investigacion Hospital Universitario La Paz, Madrid, Spain
Ismael Ghanem, Hospital Universitario La Paz, Madrid, Spain
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.