Crizotinib
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Interstitial lung disease: case report A 59-year-old woman developed interstitial lung disease (ILD) during treatment with crizotinib for stage IV lung adenocarcinoma. The woman was diagnosed with metastatic stage IVb lung adenocarcinoma T4N3M1c. Subsequently, she started receiving crizotinib 250mg twice daily [route not stated]. Twenty-one days following the initiation of crizotinib treatment, there were no adverse effects and her condition improved. However, on day 34 of the treatment, she presented with aggravated dry cough and dyspnoea. She was admitted. A chest CT demonstrated a diffusing bilateral increased ground-glass opacity and reticulation along with a medium amount of pleural effusion. She was diagnosed with pneumonia and severe respiratory failure. The woman received empirical antibiotic treatment with meropenem and vancomycin as well as non-invasive positive pressure ventilation (NIPPV). However, progressive dyspnoea and severe hypoxaemia worsened. She was then transferred to another hospital. Investigations showed following: heart rate 127 beats/min, respiratory rate 32 breaths/min, oxygen index (OI) value 82.5, leucocyte count 13.2 x 109/L, and procalcitonin level 2.28 ng/mL. Pulse oximetry showed hypoxaemia and 90% oxyhaemoglobin saturation. Sputum and blood culture did not identify any definite pathological microorganism. Echocardiography results and troponin and pro-brain-type natriuretic peptide levels were normal. A chest X-ray revealed diffusing bilateral ground-glass opacity. Based on these findings, a final diagnosis of crizotinib-induced ILD, pneumonia, and type I respiratory failure was made. She refused invasive ventilation. Treatment with crizotinib was discontinued. NIPPV was supported with an inspired oxygen fraction (FiO2) of 80%. She was initiated on methylprednisolone 40mg twice a day. However, the severe dyspnoea continued. Thereafter, bevacizumab was added and her conditions gradually improved. After treatment with methylprednisolone and bevacizumab, chest X-ray showed a decrease in ground-glass opacity. Dose of methylprednisolone was tapered to 32mg daily and eventually reduced to 4 mg/day/week. Anlotinib was administered as a second-line therapy. A repeat chest CT scans revealed that the diffuse lesions of both lungs were markedly absorbed. Seven days after anlotinib treatment, the pleural effusion had reduced significantly. On day 21 after anlotinib initiation, the hilar and mediastinum regions and the bilateral ground-glass opacity decreased. Anlotinib treatment was continued. Author comment: "She presented with severe [dyspnoea] on the 34th day, and diffuse ground-glass opacifications in her chest. A diagnosis of crizotinib-induced ILD was confirmed." Xie X, et al. Successful therapy with bevacizumab combined with corticosteroids for crizotinib-induced interstitial lung disease. Angiogenesis 22: 477-479, No. 4, Nov 2019. Available from: URL: http://doi.org/10.1007/s10456-019-09673-1 803441977 China
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