Nintedanib in the prevention of radiation-induced lung injury in patients with unresectable stage II-III NSCLC: A protocol for a randomized, multicenter, control group study
4 affiliations
- 1Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China
- 2Department of Respiratory and Critical Care Medicine, The First Hospital of Zhangjiakou, Zhangjiakou, Hebei, P.R. China
- 3Department of Radiation Oncology, Beijing Cancer Hospital, Beijing, P.R. China
- 4Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, P.R. China
Abstract
Background: Radiation-induced lung injury (RILI) is a common and dose-limiting complication in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy, especially in combination with chemotherapy and/or immunotherapy. RILI encompasses acute radiation pneumonitis (RP) and chronic pulmonary fibrosis, significantly impacting patients’ quality of life and treatment outcomes. Preclinical and clinical evidence suggests that nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF), may have preventive effects against RILI due to shared fibrotic pathways. However, prospective data on its prophylactic use remain limited. Methods: This is a randomized, multicenter, unblinded, controlled trial designed to evaluate the efficacy and safety of nintedanib in preventing RILI. A total of 66 patients with unresectable stage II-III NSCLC scheduled to receive CCRT will be enrolled from three centers in China. Eligible participants will be randomized 1:1 to either the nintedanib group or the control group. Randomization is stratified by concurrent chemotherapy regimen (etoposide-based vs. taxane-based vs. pemetrexed-based). The nintedanib group will receive oral nintedanib 150 mg twice daily, initiated 1–2 weeks before radiotherapy and continued for 12 weeks, followed by a voluntary treatment period from week 13 to week 24. The control group will receive CCRT alone without nintedanib. All patients will undergo standardized CCRT comprising platinum-based doublet chemotherapy (cisplatin or carboplatin combined with etoposide, taxanes, or pemetrexed) and radiotherapy (60 Gy/30 fractions). Immunotherapy consolidation is permitted as a viable treatment option per guideline recommendations. Primary endpoint: The incidence of grade ≥2 RILI (according to CTCAE v5.0) within 6 months after radiotherapy initiation. Secondary endpoints: Time to radiological lung injury; changes in pulmonary function (FVC%, FEV1%, DLco%); tumor response outcomes (OS, PFS, ORR); safety and tolerability; and patient-reported outcomes. This trial will provide the first prospective evidence on the efficacy of nintedanib for preventing RILI in patients with unresectable stage II-III NSCLC undergoing CCRT. The results may inform clinical practice and guide future prophylactic strategies for RILI. Trial registration: This study was registered on April 16, 2025, at the Chinese Clinical Trial Registry (No. ChiCTR2500100845). Reporting guideline: This protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines.
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BibTeX
@article{cui2026nintedanib,
title = {{Nintedanib in the prevention of radiation-induced lung injury in patients with unresectable stage II-III NSCLC: A protocol for a randomized, multicenter, control group study}},
author = {Ai Cui and Anhui Shi and Lei Deng and Yanyan Sun and Jiayi Yu and Xinrong Lian and Ziyue Zhao},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0356205},
url = {https://doi.org/10.1371/journal.pone.0356205},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Nintedanib in the prevention of radiation-induced lung injury in patients with unresectable stage II-III NSCLC: A protocol for a randomized, multicenter, control group study
AU - Ai Cui
AU - Anhui Shi
AU - Lei Deng
AU - Yanyan Sun
AU - Jiayi Yu
AU - Xinrong Lian
AU - Ziyue Zhao
PY - 2026
DA - 2026/09/03
JO - PLOS One
DO - 10.1371/journal.pone.0356205
UR - https://doi.org/10.1371/journal.pone.0356205
AB - Background: Radiation-induced lung injury (RILI) is a common and dose-limiting complication in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy, especially in combination with chemotherapy and/or immunotherapy. RILI encompasses acute radiation pneumonitis (RP) and chronic pulmonary fibrosis, significantly impacting patients’ quality of life and treatment outcomes. Preclinical and clinical evidence suggests that nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF), may have preventive effects against RILI due to shared fibrotic pathways. However, prospective data on its prophylactic use remain limited. Methods: This is a randomized, multicenter, unblinded, controlled trial designed to evaluate the efficacy and safety of nintedanib in preventing RILI. A total of 66 patients with unresectable stage II-III NSCLC scheduled to receive CCRT will be enrolled from three centers in China. Eligible participants will be randomized 1:1 to either the nintedanib group or the control group. Randomization is stratified by concurrent chemotherapy regimen (etoposide-based vs. taxane-based vs. pemetrexed-based). The nintedanib group will receive oral nintedanib 150 mg twice daily, initiated 1–2 weeks before radiotherapy and continued for 12 weeks, followed by a voluntary treatment period from week 13 to week 24. The control group will receive CCRT alone without nintedanib. All patients will undergo standardized CCRT comprising platinum-based doublet chemotherapy (cisplatin or carboplatin combined with etoposide, taxanes, or pemetrexed) and radiotherapy (60 Gy/30 fractions). Immunotherapy consolidation is permitted as a viable treatment option per guideline recommendations. Primary endpoint: The incidence of grade ≥2 RILI (according to CTCAE v5.0) within 6 months after radiotherapy initiation. Secondary endpoints: Time to radiological lung injury; changes in pulmonary function (FVC%, FEV1%, DLco%); tumor response outcomes (OS, PFS, ORR); safety and tolerability; and patient-reported outcomes. This trial will provide the first prospective evidence on the efficacy of nintedanib for preventing RILI in patients with unresectable stage II-III NSCLC undergoing CCRT. The results may inform clinical practice and guide future prophylactic strategies for RILI. Trial registration: This study was registered on April 16, 2025, at the Chinese Clinical Trial Registry (No. ChiCTR2500100845). Reporting guideline: This protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines.
SN - 1932-6203
ER -