Disease Flare after Discontinuation of Crizotinib in Anaplastic Lymphoma Kinase-Positive Lung Cancer
A 50-year-old male former smoker was found to have a left lung nodule, 25 mm in size, and chest computed tomography (CT) revealed lymph node metastases in the left hilum and mediastinum. Endobronchial ultrasound transbronchial aspiration demonstrated adenocarcinoma, and he was diagnosed with lung cancer (T1bN2M0). Two cycles of cisplatin and vinorelbine chemotherapy were administered concurrently with 50 Gy thoracic irradiation. He underwent left lower lobe resection and then received 4 cycles of adjuvant chemotherapy with carboplatin and paclitaxel; however, a single pulmonary metastasis was detected in the right lower lobe, and he received 48 Gy stereotactic radiotherapy. Subsequently, he developed mediastinal lymph node metastases. Fluorescent in situ hybridization analysis revealed that his tumor had an EML4-ALK rearrangement. The administration of crizotinib (500 mg/day) was initiated. A partial response was achieved and maintained for 10 months (fig. ); however, regrowth of the mediastinal lymph nodes was confirmed (fig. ). Crizotinib was continued for 1 month, and the size of the lymph nodes increased slightly (fig. ). At that time, crizotinib was discontinued and he participated in a randomized double-blinded phase III study of erlotinib ± Met inhibitor. Chest CT before the start of the experimental therapy (2 weeks after discontinuation of crizotinib) showed evident increase of the mediastinal lymph nodes but he did not complain of any symptoms (fig. ). However, 1 week after the start of the experimental therapy (3 weeks after discontinuation of crizotinib), he started to complain of dyspnea and dysphagia, and chest CT revealed a marked increase of the mediastinal lymph nodes accompanying marked stenosis of the bronchus and esophagus (5 weeks after discontinuation of crizotinib) (fig. ). The diagnosis of disease flare was made and readministration of crizotinib was started immediately. However, his disease progressed rapidly, and he died 2 days after starting crizotinib retreatment.