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

Joosje C Baltussen; Jonathan E Knikman; Nienke A de Glas; Mirjam de With; Arnold Baars; Geert-Jan Creemers; Helga J Droogendijk; Edward Fiets; Liselot van Iersel-Valkenburg; Caroline M P W Mandigers; Alexander L T Imholz; Marlene H W van de Poel; Frank J F Jeurissen; Machteld Wymenga; Peter Nieboer; Tessa Tigges; Eeke Wesseling; Jan H M Schellens; Jesse J Swen; Henk-Jan Guchelaar; Ron H J Mathijssen; Hans Gelderblom; Simon P Mooijaart; Annemieke Cats; Johanneke E A Portielje

doi:10.1016/j.jgo.2026.102963

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

Joosje C Baltussen
, Jonathan E Knikman
, Nienke A de Glas
, Mirjam de With
, Arnold Baars
, Geert-Jan Creemers
, Helga J Droogendijk
, Edward Fiets
, Liselot van Iersel-Valkenburg
, Caroline M P W Mandigers
, Alexander L T Imholz
, Marlene H W van de Poel
, Frank J F Jeurissen
, Machteld Wymenga
, Peter Nieboer
, Tessa Tigges
, Eeke Wesseling
, Jan H M Schellens
, Jesse J Swen
, Henk-Jan Guchelaar

Ron H J Mathijssen, Hans Gelderblom, Simon P Mooijaart, Annemieke Cats, Johanneke E A Portielje

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

INTRODUCTION: 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.

Original language	English
Article number	102963
Journal	Journal of geriatric oncology
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.jgo.2026.102963
Publication status	Published - May 2026
Externally published	Yes

Keywords

Aged
Aged, 80 and over
Antimetabolites, Antineoplastic/adverse effects
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Capecitabine/adverse effects
Colorectal Neoplasms/drug therapy
Female
Geriatric Assessment
Humans
Logistic Models
Male
Neoplasms/drug therapy
Prospective Studies

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PIIS1879406826001177Final published version, 1.38 MBLicence: CC BY

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Baltussen, J. C., Knikman, J. E., de Glas, N. A., de With, M., Baars, A., Creemers, G.-J., Droogendijk, H. J., Fiets, E., van Iersel-Valkenburg, L., Mandigers, C. M. P. W., Imholz, A. L. T., van de Poel, M. H. W., Jeurissen, F. J. F., Wymenga, M., Nieboer, P., Tigges, T., Wesseling, E., Schellens, J. H. M., Swen, J. J., ... Portielje, J. E. A. (2026). Predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy: A prospective cohort study. Journal of geriatric oncology, 17(4), Article 102963. https://doi.org/10.1016/j.jgo.2026.102963

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

abstract = "INTRODUCTION: 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.",

keywords = "Aged, Aged, 80 and over, Antimetabolites, Antineoplastic/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Capecitabine/adverse effects, Colorectal Neoplasms/drug therapy, Female, Geriatric Assessment, Humans, Logistic Models, Male, Neoplasms/drug therapy, Prospective Studies",

author = "Baltussen, \{Joosje C\} and Knikman, \{Jonathan E\} and \{de Glas\}, \{Nienke A\} and \{de With\}, Mirjam and Arnold Baars and Geert-Jan Creemers and Droogendijk, \{Helga J\} and Edward Fiets and \{van Iersel-Valkenburg\}, Liselot and Mandigers, \{Caroline M P W\} and Imholz, \{Alexander L T\} and \{van de Poel\}, \{Marlene H W\} and Jeurissen, \{Frank J F\} and Machteld Wymenga and Peter Nieboer and Tessa Tigges and Eeke Wesseling and Schellens, \{Jan H M\} and Swen, \{Jesse J\} and Henk-Jan Guchelaar and Mathijssen, \{Ron H J\} and Hans Gelderblom and Mooijaart, \{Simon P\} and Annemieke Cats and Portielje, \{Johanneke E A\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors.",

year = "2026",

month = may,

doi = "10.1016/j.jgo.2026.102963",

language = "English",

volume = "17",

journal = "Journal of geriatric oncology",

issn = "1879-4068",

publisher = "Elsevier Limited",

number = "4",

}

Baltussen, JC, Knikman, JE, de Glas, NA, de With, M, Baars, A, Creemers, G-J, Droogendijk, HJ, Fiets, E, van Iersel-Valkenburg, L, Mandigers, CMPW, Imholz, ALT, van de Poel, MHW, Jeurissen, FJF, Wymenga, M, Nieboer, P, Tigges, T, Wesseling, E, Schellens, JHM, Swen, JJ, Guchelaar, H-J, Mathijssen, RHJ, Gelderblom, H, Mooijaart, SP, Cats, A & Portielje, JEA 2026, 'Predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy: A prospective cohort study', Journal of geriatric oncology, vol. 17, no. 4, 102963. https://doi.org/10.1016/j.jgo.2026.102963

TY - JOUR

T1 - Predictors of poor treatment tolerability in older patients receiving fluoropyrimidine-based chemotherapy

T2 - A prospective cohort study

AU - Baltussen, Joosje C

AU - Knikman, Jonathan E

AU - de Glas, Nienke A

AU - de With, Mirjam

AU - Baars, Arnold

AU - Creemers, Geert-Jan

AU - Droogendijk, Helga J

AU - Fiets, Edward

AU - van Iersel-Valkenburg, Liselot

AU - Mandigers, Caroline M P W

AU - Imholz, Alexander L T

AU - van de Poel, Marlene H W

AU - Jeurissen, Frank J F

AU - Wymenga, Machteld

AU - Nieboer, Peter

AU - Tigges, Tessa

AU - Wesseling, Eeke

AU - Schellens, Jan H M

AU - Swen, Jesse J

AU - Guchelaar, Henk-Jan

AU - Mathijssen, Ron H J

AU - Gelderblom, Hans

AU - Mooijaart, Simon P

AU - Cats, Annemieke

AU - Portielje, Johanneke E A

PY - 2026/5

Y1 - 2026/5

N2 - INTRODUCTION: 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.

AB - INTRODUCTION: 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.

KW - Aged

KW - Aged, 80 and over

KW - Antimetabolites, Antineoplastic/adverse effects

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Capecitabine/adverse effects

KW - Colorectal Neoplasms/drug therapy

KW - Female

KW - Geriatric Assessment

KW - Humans

KW - Logistic Models

KW - Male

KW - Neoplasms/drug therapy

KW - Prospective Studies

U2 - 10.1016/j.jgo.2026.102963

DO - 10.1016/j.jgo.2026.102963

M3 - Article

C2 - 41932292

SN - 1879-4068

VL - 17

JO - Journal of geriatric oncology

JF - Journal of geriatric oncology

IS - 4

M1 - 102963

ER -

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

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