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Multicenter Study
. 2025 Jun;26(4):324-330.e3.
doi: 10.1016/j.cllc.2025.03.010. Epub 2025 Mar 26.

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

Mart P Kicken  1 , Rob Ter Heine  2 , Intissar Azarfane  3 , Nikki de Rouw  4 , Fenna de Vries  5 , Bas J M Peters  6 , Nienke A G Lankheet  7 , Frank Eektimmerman  8 , Tim Beerden  9 , Eric J F Franssen  10 , Lisanne L Krens  11 , Cor H van der Leest  12 , Arthur A J Smit  13 , Albert J Polman  14 , Laura C Vermeer  15 , John W G van Putten  16 , Ben E E M van den Borne  17 , Michel M van den Heuvel  18 , Maarten J Deenen  19
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Free article
Multicenter Study

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

Mart P Kicken et al. Clin Lung Cancer. 2025 Jun.
Free article

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: Chemotherapy; Hematological toxicity; Impaired renal function; Real-world data; Treatment discontinuation.

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Conflict of interest statement

Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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