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April 4, 2026Open Access

Predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy: A prospective cohort study

Key Points

This study aims to identify predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy.
Prospective, multicentre, non-randomized cohort study
Included patients aged ≥70 years receiving fluoropyrimidine-based chemotherapy
Participants underwent geriatric assessments across various domains
Analysed predictors of poor treatment tolerability using logistic regression
31% of patients experienced poor treatment tolerability within the first two cycles
Patients with deficits in 3–4 geriatric domains had an odds ratio of 4.03 for poor tolerability
Combination chemotherapy was associated with an odds ratio of 2.83 for poor tolerability

Abstract

AbstractIntroduction Although fluoropyrimidines are widely prescribed to older patients, studies investigating predictors for chemotherapy intolerance in this patient population are scarce. Therefore, we aimed to identify predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy. Materials and methods Patients aged ≥70 years who received fluoropyrimidine-based chemotherapy were selected from the prospective, multicentre, non-randomized Alpe2U study. Before treatment initiation, participants underwent a geriatric assessment investigating the somatic, nutritional, functional, and mental domains. Predictors of the composite endpoint "poor treatment tolerability," defined as either Common Toxicity Criteria Adverse Events (CTCAE) grade 3–5 chemotherapy-related toxicity, dose reduction, or treatment discontinuation within the first two cycles, were analysed using uni- and multivariable logistic regression models. Results Of the 194 included patients, median age was 75 (interquartile range 73–79) years and the most common tumour types were colorectal (60%) and esophagogastric (19%) cancer. Most patients (89%) received capecitabine-based chemotherapy. Poor treatment tolerability within the first two cycles was seen in 31% of patients. In multivariable analyses, associations with poor treatment tolerability were found for deficits in 3–4 geriatric domains compared with 0 deficits (odds ratio OR 4.03, 95% confidence interval CI 1.09–14.97, p = 0.04) and for combination chemotherapy (OR 2.83, 95% CI 1.31–6.09, p = 0.008). Discussion Having deficits in multiple geriatric domains and combination chemotherapy were predictors of poor treatment tolerability within the first two cycles in older patients treated with fluoropyrimidine-based chemotherapy. These findings highlight the importance of a geriatric assessment before fluoropyrimidine administration to estimate risk of treatment intolerance.

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