Title: Evaluation of Early Onset Severe Treatment-related Adverse Events for Fluoropyrimidine-based Chemotherapy
Authors: Alexandria Rakestraw, Alex Balkcom, Rodna Larson
Background:
Fluoropyrimidines such as 5-fluorouracil (5-FU) and capecitabine are commonly used in the treatment of solid tumors. Fluoropyrimidines work by inhibiting thymidylate synthase and incorporating the metabolites into DNA synthesis, disrupting the creation of cancerous cells.
The toxicities of fluoropyrimidines are typically seen within the first few cycles of treatment. Toxicities can occur due to the mechanism of action of fluoropyrimidines or can occur due to genetic mutations but can be enhanced by genetic mutations. Fluoropyrimidines are metabolized by dihydropyrimidine dehydrogenase. Dose reductions are based on variants to avoid potential accumulation and therefore potential toxicities.
This retrospective chart review was designed to identify CTCAE grade 3-5 toxicities in patients receiving fluoropyrimidine-based treatments, explain dose modifications secondary to genotypic variation, and understand the current practice of genotype testing prior to receiving these chemotherapeutic agents.
Methods:
This single-center, retrospective, observational chart-review was conducted at our institution from January 1, 2023, to February
[RA1] 1, 2026. Adults
>18 were eligible to be included in this study if they received 5-FU or capecitabine for any solid tumor and if the first dose of either medication was given within the study period. Patients were excluded from the study if the patient was being treated in a clinical trial.
The primary objective of the study was to determine the incidence and onset of grade 3-5 fluoropyrimidine-related toxicity within the first three cycles of treatment in correlation with DPYD genotype status. The specified narrowed toxicities include diarrhea, mucositis, cardiotoxicity, palmar plantar erythrodysesthesia, and pancytopenia (thrombocytopenia and neutropenia). Secondary endpoints included identification of genotypic variants, retrospective dose adjustments, time to death, and genotype testing turnaround times.
Results:
Among 85 patients treated with fluoropyrimidine-based chemotherapy (5-FU, n=51; capecitabine, n=34), DPYD genetic testing rates were low overall, yet patients tested prior to treatment initiation experienced a 59% reduction in grade 3+ toxicity events compared to untested patients (10.0% vs 24.6%, RR=0.41).
Conclusions: These data suggest that pre-treatment DPYD screening may reduce severe fluoropyrimidine-related toxicity, though the difference did not reach statistical significance given the limited sample size.
Testing is available as a blood draw that has an average 9-day turnaround time.
