Abstract
BackgroundCrizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood.Case presentationWe first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died.ConclusionsThe present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.
Highlights
Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a c-ros oncogene 1 (ROS1) rearrangement
The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality
Crizotinib is a multi-target inhibitor, which was granted a full approval by the Food and Drug Administration (FDA) for the treatment of advanced non-small-cell lung cancer (NSCLC) patients with a ROS1 rearrangement in March 2016
Summary
Advanced non-small-cell lung cancer in patients with ROS1 rearrangements, treated with crizotinib, may be accompanied by fatal ILD in the initial period. Davies KD, Mahale S, Astling DP, et al Resistance to ROS1 inhibition mediated by EGFR pathway activation in non-small cell lung cancer. Ethics approval and consent to participate The study was performed in accordance with the Declaration of Helsinki and was approved by the Lihuili Hospital Cancer Centre Ethics Review Board. Author details 1Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, No 57, Xin’ning Road, Ningbo 315041, China. Author details 1Department of Respiratory Medicine, Lihuili Hospital, Ningbo Medical Center, No 57, Xin’ning Road, Ningbo 315041, China. 2Department of Radiation Oncology, Lihuili Hospital, Ningbo Medical Center, Ningbo 315041, China. 3Department of Radiology, Lihuili Hospital, Ningbo Medical Center, Ningbo 315041, China. 4Department of Thoracic Surgery, Lihuili Hospital, Ningbo Medical Center, Ningbo 315041, China. 5Department of Diagnosis, Ningbo Diagnostic Pathology Center, No 79, Huan’cheng Road, Ningbo 315021, China
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