The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study

Mart P Kicken; Rob Ter Heine; Intissar Azarfane; Nikki de Rouw; Fenna de Vries; Bas J M Peters; Nienke A G Lankheet; Frank Eektimmerman; Tim Beerden; Eric J F Franssen; Lisanne L Krens; Cor H van der Leest; Arthur A J Smit; Albert J Polman; Laura C Vermeer; John W G van Putten; Ben E E M van den Borne; Michel M van den Heuvel; Maarten J Deenen

doi:10.1016/j.cllc.2025.03.010

The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study

Mart P Kicken^*
, Rob Ter Heine
, Intissar Azarfane
, Nikki de Rouw
, Fenna de Vries
, Bas J M Peters
, Nienke A G Lankheet
, Frank Eektimmerman
, Tim Beerden
, Eric J F Franssen
, Lisanne L Krens
, Cor H van der Leest
, Arthur A J Smit
, Albert J Polman
, Laura C Vermeer
, John W G van Putten
, Ben E E M van den Borne
, Michel M van den Heuvel
, Maarten J Deenen

^*Corresponding author for this work

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

Abstract

Purpose: Pemetrexed is a key drug in the immunochemotherapy of non-small cell lung cancer (NSCLC). However, its use is contraindicated in patients with renal impairment due to severe toxicity risks. As renal impairment is common in lung cancer patients, healthcare professionals face a dilemma between withholding effective treatment and risking toxicity. Real-world data on pemetrexed toxicity may aid in this decision. The primary objective of this study was to describe the toxicity profile of pemetrexed treatment in NSCLC patients with renal impairment. Patients and methods: This multicenter, descriptive, retrospective study was conducted across 9 hospitals in the Netherlands between 2015 and 2024. Patients included had a diagnosis of NSCLC, received ≥ 1 cycle of standard dose pemetrexed, and had a baseline creatinine clearance (CrCL)<45 mL/min. Data were collected on patient and treatment characteristics, hematological and nonhematological toxicity incidences, treatment discontinuation, dose reduction, and treatment-related hospitalization. Results: Forty-four patients were included, with median CrCL 41.1 mL/min (interquartile range: 35.0-43.9). Thirty-one patients (70%) did not finish 4 cycles of pemetrexed treatment, with 14 patients (45%) discontinuing due to pemetrexed-associated toxicity. More than half of patients (n = 28; 64%) were hospitalized due to treatment-related toxicity. Seventeen patients (39%) developed grade 3-4 neutropenia and leukopenia. Gastro-intestinal toxicity grade 3 to 4 occurred in fifteen (34%) patients. Conclusion: Pemetrexed treatment of NSCLC patients with moderate renal impairment was associated with high incidence of hematological toxicity, hospitalization, dose reduction, and treatment discontinuation. These results highlight the necessity of developing new treatment regimens to enable safe pemetrexed-based immunochemotherapy in NSCLC patients with renal impairment.

Original language	English
Pages (from-to)	324-330.e3
Journal	Clinical lung cancer
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.cllc.2025.03.010
Publication status	Published - Jun 2025
Externally published	Yes

Keywords

Aged
Carcinoma, Non-Small-Cell Lung/drug therapy
Female
Follow-Up Studies
Humans
Lung Neoplasms/drug therapy
Male
Middle Aged
Pemetrexed/adverse effects
Prognosis
Renal Insufficiency
Retrospective Studies

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10.1016/j.cllc.2025.03.010

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Kicken, M. P., Ter Heine, R., Azarfane, I., de Rouw, N., de Vries, F., Peters, B. J. M., Lankheet, N. A. G., Eektimmerman, F., Beerden, T., Franssen, E. J. F., Krens, L. L., van der Leest, C. H., Smit, A. A. J., Polman, A. J., Vermeer, L. C., van Putten, J. W. G., van den Borne, B. E. E. M., van den Heuvel, M. M., & Deenen, M. J. (2025). The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study. Clinical lung cancer, 26(4), 324-330.e3. https://doi.org/10.1016/j.cllc.2025.03.010

@article{9fe5dd6104c94c0b93c5bdadf2eb5c69,

title = "The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study",

abstract = "Purpose: Pemetrexed is a key drug in the immunochemotherapy of non-small cell lung cancer (NSCLC). However, its use is contraindicated in patients with renal impairment due to severe toxicity risks. As renal impairment is common in lung cancer patients, healthcare professionals face a dilemma between withholding effective treatment and risking toxicity. Real-world data on pemetrexed toxicity may aid in this decision. The primary objective of this study was to describe the toxicity profile of pemetrexed treatment in NSCLC patients with renal impairment. Patients and methods: This multicenter, descriptive, retrospective study was conducted across 9 hospitals in the Netherlands between 2015 and 2024. Patients included had a diagnosis of NSCLC, received ≥ 1 cycle of standard dose pemetrexed, and had a baseline creatinine clearance (CrCL)<45 mL/min. Data were collected on patient and treatment characteristics, hematological and nonhematological toxicity incidences, treatment discontinuation, dose reduction, and treatment-related hospitalization. Results: Forty-four patients were included, with median CrCL 41.1 mL/min (interquartile range: 35.0-43.9). Thirty-one patients (70\%) did not finish 4 cycles of pemetrexed treatment, with 14 patients (45\%) discontinuing due to pemetrexed-associated toxicity. More than half of patients (n = 28; 64\%) were hospitalized due to treatment-related toxicity. Seventeen patients (39\%) developed grade 3-4 neutropenia and leukopenia. Gastro-intestinal toxicity grade 3 to 4 occurred in fifteen (34\%) patients. Conclusion: Pemetrexed treatment of NSCLC patients with moderate renal impairment was associated with high incidence of hematological toxicity, hospitalization, dose reduction, and treatment discontinuation. These results highlight the necessity of developing new treatment regimens to enable safe pemetrexed-based immunochemotherapy in NSCLC patients with renal impairment.",

keywords = "Aged, Carcinoma, Non-Small-Cell Lung/drug therapy, Female, Follow-Up Studies, Humans, Lung Neoplasms/drug therapy, Male, Middle Aged, Pemetrexed/adverse effects, Prognosis, Renal Insufficiency, Retrospective Studies",

author = "Kicken, \{Mart P\} and \{Ter Heine\}, Rob and Intissar Azarfane and \{de Rouw\}, Nikki and \{de Vries\}, Fenna and Peters, \{Bas J M\} and Lankheet, \{Nienke A G\} and Frank Eektimmerman and Tim Beerden and Franssen, \{Eric J F\} and Krens, \{Lisanne L\} and \{van der Leest\}, \{Cor H\} and Smit, \{Arthur A J\} and Polman, \{Albert J\} and Vermeer, \{Laura C\} and \{van Putten\}, \{John W G\} and \{van den Borne\}, \{Ben E E M\} and \{van den Heuvel\}, \{Michel M\} and Deenen, \{Maarten J\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jun,

doi = "10.1016/j.cllc.2025.03.010",

language = "English",

volume = "26",

pages = "324--330.e3",

journal = "Clinical lung cancer",

issn = "1525-7304",

publisher = "Elsevier",

number = "4",

}

Kicken, MP, Ter Heine, R, Azarfane, I, de Rouw, N, de Vries, F, Peters, BJM, Lankheet, NAG, Eektimmerman, F, Beerden, T, Franssen, EJF, Krens, LL, van der Leest, CH, Smit, AAJ, Polman, AJ, Vermeer, LC, van Putten, JWG, van den Borne, BEEM, van den Heuvel, MM & Deenen, MJ 2025, 'The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study', Clinical lung cancer, vol. 26, no. 4, pp. 324-330.e3. https://doi.org/10.1016/j.cllc.2025.03.010

TY - JOUR

T1 - The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment

T2 - A Retrospective Cohort Study

AU - Kicken, Mart P

AU - Ter Heine, Rob

AU - Azarfane, Intissar

AU - de Rouw, Nikki

AU - de Vries, Fenna

AU - Peters, Bas J M

AU - Lankheet, Nienke A G

AU - Eektimmerman, Frank

AU - Beerden, Tim

AU - Franssen, Eric J F

AU - Krens, Lisanne L

AU - van der Leest, Cor H

AU - Smit, Arthur A J

AU - Polman, Albert J

AU - Vermeer, Laura C

AU - van Putten, John W G

AU - van den Borne, Ben E E M

AU - van den Heuvel, Michel M

AU - Deenen, Maarten J

PY - 2025/6

Y1 - 2025/6

N2 - Purpose: Pemetrexed is a key drug in the immunochemotherapy of non-small cell lung cancer (NSCLC). However, its use is contraindicated in patients with renal impairment due to severe toxicity risks. As renal impairment is common in lung cancer patients, healthcare professionals face a dilemma between withholding effective treatment and risking toxicity. Real-world data on pemetrexed toxicity may aid in this decision. The primary objective of this study was to describe the toxicity profile of pemetrexed treatment in NSCLC patients with renal impairment. Patients and methods: This multicenter, descriptive, retrospective study was conducted across 9 hospitals in the Netherlands between 2015 and 2024. Patients included had a diagnosis of NSCLC, received ≥ 1 cycle of standard dose pemetrexed, and had a baseline creatinine clearance (CrCL)<45 mL/min. Data were collected on patient and treatment characteristics, hematological and nonhematological toxicity incidences, treatment discontinuation, dose reduction, and treatment-related hospitalization. Results: Forty-four patients were included, with median CrCL 41.1 mL/min (interquartile range: 35.0-43.9). Thirty-one patients (70%) did not finish 4 cycles of pemetrexed treatment, with 14 patients (45%) discontinuing due to pemetrexed-associated toxicity. More than half of patients (n = 28; 64%) were hospitalized due to treatment-related toxicity. Seventeen patients (39%) developed grade 3-4 neutropenia and leukopenia. Gastro-intestinal toxicity grade 3 to 4 occurred in fifteen (34%) patients. Conclusion: Pemetrexed treatment of NSCLC patients with moderate renal impairment was associated with high incidence of hematological toxicity, hospitalization, dose reduction, and treatment discontinuation. These results highlight the necessity of developing new treatment regimens to enable safe pemetrexed-based immunochemotherapy in NSCLC patients with renal impairment.

AB - Purpose: Pemetrexed is a key drug in the immunochemotherapy of non-small cell lung cancer (NSCLC). However, its use is contraindicated in patients with renal impairment due to severe toxicity risks. As renal impairment is common in lung cancer patients, healthcare professionals face a dilemma between withholding effective treatment and risking toxicity. Real-world data on pemetrexed toxicity may aid in this decision. The primary objective of this study was to describe the toxicity profile of pemetrexed treatment in NSCLC patients with renal impairment. Patients and methods: This multicenter, descriptive, retrospective study was conducted across 9 hospitals in the Netherlands between 2015 and 2024. Patients included had a diagnosis of NSCLC, received ≥ 1 cycle of standard dose pemetrexed, and had a baseline creatinine clearance (CrCL)<45 mL/min. Data were collected on patient and treatment characteristics, hematological and nonhematological toxicity incidences, treatment discontinuation, dose reduction, and treatment-related hospitalization. Results: Forty-four patients were included, with median CrCL 41.1 mL/min (interquartile range: 35.0-43.9). Thirty-one patients (70%) did not finish 4 cycles of pemetrexed treatment, with 14 patients (45%) discontinuing due to pemetrexed-associated toxicity. More than half of patients (n = 28; 64%) were hospitalized due to treatment-related toxicity. Seventeen patients (39%) developed grade 3-4 neutropenia and leukopenia. Gastro-intestinal toxicity grade 3 to 4 occurred in fifteen (34%) patients. Conclusion: Pemetrexed treatment of NSCLC patients with moderate renal impairment was associated with high incidence of hematological toxicity, hospitalization, dose reduction, and treatment discontinuation. These results highlight the necessity of developing new treatment regimens to enable safe pemetrexed-based immunochemotherapy in NSCLC patients with renal impairment.

KW - Aged

KW - Carcinoma, Non-Small-Cell Lung/drug therapy

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Lung Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Pemetrexed/adverse effects

KW - Prognosis

KW - Renal Insufficiency

KW - Retrospective Studies

U2 - 10.1016/j.cllc.2025.03.010

DO - 10.1016/j.cllc.2025.03.010

M3 - Article

C2 - 40263048

SN - 1525-7304

VL - 26

SP - 324-330.e3

JO - Clinical lung cancer

JF - Clinical lung cancer

IS - 4

ER -

The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study

Abstract

Keywords

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