Osimertinib
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Drug-induced lung injury: case report A 76-year-old man developed drug-induced lung injury during treatment with osimertinib for lung adenocarcinoma. The man, who had history of hypertension, atrial fibrillation and colon cancer surgery, presented with abnormal shadow in the chest. He had been diagnosed with lung adenocarcinoma cT2N3M1c stage IVB in March. Additionally, he had cervical spinal cord compression due to cervical spine metastasis. Therefore, he had received radiation therapy to the cervical and thoracic vertebrae and mediastinal hilar. As his cancer had epidermal growth factor receptor (EGFR) positive mutation, he had started receiving osimertinib 80mg daily [route not stated] from April. The dose of osimertinib had been reduced to 40mg daily due to liver disorder; however, both primary and metastatic lesions were shrunk. At the end of June, he had developed radiation pneumonia in the lung field adjacent to the mediastinum. Therefore, he had started receiving prednisolone. During routine check-up in the December of the same year (36 weeks from the initiation of osimertinib), an infiltrative shadow in the lower left lung field was noted. Therefore, he was hospitalised (current presentation). He was ex-smoker and alcohol user. His vital signs were as follows: blood pressure 145/61mm Hg, body temperature 36.3oC, pulse rate 54 times/minute/adjustment, respiration rate 12 times/minute and percutaneous arterial oxygen saturation 92% at room air. Physical examination revealed fine crackling sound in the lower left lung field. Also, numbness in his left finger and motor paralysis were noted. No other abnormal findings were detected. Laboratory investigations revealed slight increase in CRP. No increase in tumour markers or KL-6 was noted. On admission, chest radiograph showed an infiltrative shadow in the lower left lung field. Fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed remarkable decrease in FDG accumulation in the mediastinal lymph nodes, primary lesion, metastases to right adrenal and multiple metastases to bone compared to the time of diagnosis. Also, a new FDG accumulation lesion was found in the left lower lobe. Chest CT showed an infiltrative shadow in the lower lobe of the left lung. Histopathological analysis of sample obtained from transbronchial lung biopsy showed granulomatous tissue hyperplasia of the alveoli and lymphocyte infiltration, which were significant with organising pneumonia. A bronchoalveolar lavage fluid cultures were negative for infectious aetiologies, and there was no growth of atypical cells, which ruled out the possibility of exacerbation of infectious pneumonia and lung cancer. Thereafter, it was noted that the localisation of the new shadow did not coincide with the radiation field and it appeared 9 months after irradiation, which indicated that it was not a typical radiation pneumonia. Therefore, drug-induced lung injury due to osimertinib was suspected. Drug withdrawal was planned; however, there was a remarkable tumour-shrinking effect, without re
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