Background: High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.
Methods: We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic regression modeling was performed to estimate adjusted odds ratios according to patient characteristics.
Results: Among 1,998 patients included in the study, 167 (8%) developed grade ≥3 CIPN. Grade ≥3 CIPN was associated with higher body mass index (BMI) (P = .01), sex (7% for men vs 10% for women; P = .005), age (11% for ≥65 years vs 7% for <65 years; P < .001), chemotherapy regimen (P = .01), and greater number treatment cycles (P < .001). In a multivariate model, regimens featuring higher doses of paclitaxel or cisplatin, greater number of chemotherapy cycles, female sex, greater age, and higher BMI remained independently associated with grade ≥3 CIPN.
Conclusions: High-grade CIPN is associated with chemotherapy type and exposure, female sex, greater age, and elevated BMI. Given the ongoing use of cytotoxic agents in established and new (eg, antibody-drug conjugates) treatment regimens, these findings have implications for patient monitoring and treatment selection.
Keywords: CIPN; chemotherapy; neuropathy; nonsmall cell lung cancer; toxicity.
© The Author(s) 2025. Published by Oxford University Press.