ArticleFundamental & clinical pharmacology2025
Severe fluoropyrimidine toxicity in older adults with cancer with DPYD wild type.
Article in Fundamental & clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Model-based meta-analysis of individual patient data for the characterization of intravenous 5-fluorouracil population pharmacokinetics.Cancer chemotherapy and pharmacology · 2026Pooled it
- DPYD and UGT1A1 Genotype-Based Dosing for Fluoropyrimidines and Irinotecan Chemotherapy: Variant-Specific Impact on Treatment Intensity and Toxicity.International journal of cancer · 2026Article
- Severe fluoropyrimidine toxicity in older adults with cancer with DPYD wild type.Fundamental & clinical pharmacology · 2025Article
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15 authors.
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Abstract
backgroundDespite the implementation of DPYD genotype-guided dosing, approximately 1 in 3 patients receiving fluoropyrimidine-containing chemotherapy continues to experience severe toxicity. While clinical studies have demonstrated a favorable tolerance among highly selected fit older adults, real-world studies have shown an increased risk of toxicity.
objectiveTo identify predictors of severe toxicity or treatment deintensification in older DPYD wild-type adults receiving fluoropyrimidine-containing chemotherapy.
methodPatients wild type for four tested DPYD variants, aged ≥65 years, who participated in a prospective clinical trial investigating genotype-guided individualized fluoropyrimidine dosing, were eligible for the study. The association between tumor-, treatment-, and patient-related characteristics and the occurrence of severe toxicity (grade ≥3, CTCAE v5.0) was analyzed in univariate and multivariate logistic regression analyses. The same analyses were performed for a composite endpoint of severe toxicity or treatment deintensification (including dose reduction, cycle delay, or discontinuation).
resultsA total of 311 patients were included. Median age was 71.2 years and 58.8% were male. Grade ≥3 toxicity occurred in 23.2% of patients. In multivariate analysis, none of the characteristics studied were significantly associated with the occurrence of grade ≥3 toxicity. The composite endpoint occurred in 41.2% of patients and was associated with the use of full dose monotherapy in multivariate analysis.
conclusionDespite DPYD genotype-based dosing, grade ≥3 toxicity and treatment deintensification frequently occur in older patients treated with fluoropyrimidine chemotherapy. No patient-related variables were found to be associated with grade ≥3 toxicity, but treatment with dose-reduced monotherapy resulted in fewer treatment deintensification or severe toxicity events.
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