A 62-year-old man, complaining of fever and shortness of breath >1 year subsequent to surgery for right-sided NSCLC, was admitted to the First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China). In July 2010, the patient was revealed to have a lesion in the right upper lobe of the lung in a physical examination. In August 2010, upper right lobe resection and mediastinal lymph node dissections were performed. The tumor measured 3.5x3.0x2.0 cm. The pathological analysis of the resected upper right lung showed that the patient was suffering from differentiated adenocarcinoma and bronchioloalveolar carcinoma. The lung membrane, bronchial stump and lung hilar lymph nodes were not invaded (stage IB, pT2aN0M0). Following surgery, the patient did not receive any further treatment. In June 2011, the patient started to cough with obvious incentive; white phlegm was apparent, accompanied by intermittent bloody sputum. A chest computed tomography (CT) scan (Fig. 1A) showed multiple small nodules scattered throughout the patient's lungs, suggesting pulmonary metastasis. The patient developed a progressive disease following four cycles of chemotherapy with a pemetrexed-cisplatin regimen, starting in July 2011 (Fig. 1B). The EGFR gene mutation test showed a deletion in exon 19; however, there were no mutations in exons 18, 20 or 21. The K-RAS gene mutation test showed no mutations in exons 13 or 61. In November 2011, daily treatment with oral gefitinib (250 mg/day) was initiated and the patient achieved a partial response one month subsequently (Fig. 1C). However, 60 days subsequent to the initiation of the gefitinib treatment, the patient developed fever, an aggravated dry cough and dyspnea. On the visit to our clinic, the patient appeared acutely ill and presented with dyspnea, with a body temperature fluctuating between 37.6 and 38.8 C. The patient was previously healthy and reported no history of chronic diseases, such as hypertension, heart disease and diabetes, and acute or chronic infection, such as hepatitis and tuberculosis. He had a smoking history of >20 years (40 cigarettes a day) and had quit smoking for 13 years, with a smoking index of 800. Physical examination showed that the patient had a body temperature of 38.3 C, a pulse rate of 124 beats/min, a respiratory rate of 41 breaths/min and a blood pressure of 130/80 mmHg. Hypoxemia and an oxyhemoglobin saturation of 88% were detected using pulse oximetry and visible, large erythema and pimples, with scales and itching, were observed around the ankles and the dorsal surfaces of the elbow joint. The examination results are listed in Table I. A chest CT scan showed interstitial inflammation of the lungs, bilateral pleural effusion and an adverse swelling of the lungs (Fig. 1D). The patient was admitted with suspected gefitinib-induced interstitial pneumonitis.
Following admission, gefitinib administration was discontinued immediately. No evidence of infection or the presence of pathological microorganisms was found in either the sputum or blood culture (Table I), while chest CT revealed a diffuse ground-glass opacity over the whole right and left lungs. A lung biopsy revealed interstitial pneumonia, with a widening of the alveolar septa and alveolar epithelial hyperplasia. A small quantity of inflammatory exudate was observed in the alveolar cavity (Fig. 1H and I). The patient was treated with inhaled oxygen, electrocardiography, cefoperazone/sulbactam (3.0 g twice daily; to provide resistance to infection), doxofylline (0.2 g once daily; to relieve coughing), high-dose methylprednisolone (1,000 mg daily for three days), inhalation of expectorant and dexamethasone (5.0 mg twice daily), acetylcysteine (600 mg/Tid; to prevent pulmonary fibrosis) and an infusion of protein. Therapies for the protection of the liver and gastric mucosa, improvement of the immune system, prevention of fungal infections (fluorouracil mouthwash) and adjustment of the intestinal flora were also administered to the patient. The patient's dyspnea and hypoxemia improved significantly in three days. The results of the laboratory tests taken 10 days subsequent to the treatments are presented in Table I. The follow-up high-resolution CT scan (Fig. 1E) showed the total resolution of the ground-glass lesions and the absorption of the right-side pleural fluid. Based on the patient's recovery, gefitinib treatment was reinitiated, under close observation. The gefitinib dosage was adjusted to 250 mg, taken once every two days. In addition, acetylcysteine was administered to prevent pulmonary fibrosis. No significant adverse response was detected in the patient. One month later, the follow-up chest CT (Fig. 1F) showed no interstitial pneumonia recurrence or tumor progression.
Based on the case reports and literature reviews on interstitial pneumonia published in Western countries and China between 2003 and 2011, the clinical characteristics of gefitinib-induced interstitial pneumonia were preliminarily analyzed. The results are presented in Table II.