[Safe treatment of lung squamous cell carcinoma with nanoparticle albumin-bound Paclitaxel in a patient with a previous hypersensitivity reaction after docetaxel administration].

A 61-year-old man was diagnosed with lung squamous cell carcinoma in the lower lobe of the right lung. He had received first-line chemotherapy consisting of cisplatin and docetaxel (DTX); however, an allergic/hypersensitivity reaction occurred shortly after administration of the second course of DTX. Thirty-nine months later, he received nanoparticle albumin-bound paclitaxel (nab-PTX) as sixth-line chemotherapy, which did not produce a hypersensitivity reaction. Hypersensitivity after DTX administration may have been due to the DTX vehicle. Therefore, nab-PTX administered under close supervision is a valid therapeutic option in similar cases.

[A case of lung adenocarcinoma effectively treated with sivelestat and corcicosteroid for drug-induced lung disease due to gefitinib].

A 70-year-old Japanese man was re-admitted because of relapse of adenocarcinoma of the lung. He received daily administration of gefitinib as second-line chemotherapy. He was given a diagnosis of drug-induced lung disease due to gefitinib on day 6 because of hypoxemia and ground glass opacities in the bilateral lung fields. There was no response to corticosteroid pulse therapy. Continuous administration of sivelestat was intravenously added from day 9. Although mechanical ventilation was required for 10 days, lung infiltrates and hypoxia gradually improved. Sivelestat and corcicosteroid was apparently effective in this case and may be useful treatment for drug-induced lung disease due to gefitinib.

[Case of bilateral pneumothorax observed during the administration of gefitinib for lung adenocarcinoma with multiple pulmonary metastases].

A 61-year-old woman who had never smoked was given a diagnosis of adenocarcinoma of the lung with multiple pulmonary metastases. Systemic chemotherapy consisting of carboplatin and paclitaxel was not effective, thereafter daily oral administration of gefitinib was initiated. Six days later, bilateral pneumothorax was found. The extent of the pneumothorax was slight and she recovered without drainage within about one month although treatment of gefitinib was restarted. Gefitinib was effective for lung cancer in this case. Bilateral pneumothorax is a rare complication of chemotherapy for lung cancer. Only 3 such cases under treatment with gefitinib were reported in Japan.

[A case of spontaneous resolution of sarcoidosis with primary pulmonary cavitations].

On routine physical checkup, a 27-year-old man with productive cough was found to have multiple nodules with cavitation in the bilateral lung fields and mediastinal and hilar lymph adenopathy on chest X-ray film and CT scan. Serum levels of angiotensin converting enzyme and lysozyme were high. Tuberculin reaction was negative. Non-caseous epitheloid granulomas were confirmed in the bronchial wall specimens obtained by trans-bronchial biopsy. The number of lymphocytes and the CD4/CD8 ratio of lymphocytes in bronchoalveolar lavage fluid was increased. Therefore, pulmonary sarcoidosis was diagnosed, and the lung nodules with cavitation were considered due to sarcoidosis. The walls of the cavitations gradually thinned and had almost completely vanished after 6 months of careful observation without steroid therapy.

[A case of pneumonitis suspected to be induced by Oseltamivir].

A 33-year-old man had a high fever and was given Cefcapene and Oseltamivir without a definite diagnosis of influenza. Three days later an abnormal chest shadow was pointed out. Chest CT revealed ground-glass opacities and air-space consolidation in bilateral lung fields. Although he was given antibiotics, lung infiltrates increased and his symptoms worsened. Therefore, he was transferred to our hospital. Corticosteroid pulse-therapy resulted in prompt improvement of chest infiltrates and his symptoms. The drug-induced lymphocyte stimulating test results indicated 170% of oseltamivir and 150% of cefcapene. Considering the clinical course and laboratory data, this was probably drug-induced lung injury caused by oseltamivir.

[Case of lung cancer with chylothorax].

A 42-year-old man had swelling in the right side of the neck, cough and chest pain. On admission, an abnormal shadow was detected in the right upper lung field and squamous cell carcinoma of the lung with superior vena cava (SVC) syndrome was diagnosed. Concurrent radiotherapy and systemic chemotherapy consisting of cisplatin and vinorelbine induced a partial response. At 15 months after diagnosis, he was re-admitted because of bilateral pleural effusion and facial edema due to relapse of SVC syndrome. Examination of the milky right pleural effusion revealed chylothorax (959mg/dl of beta-lipoprotein and 675mg/dl of triglyceride). The right effusion was finally controlled by pleurodesis with OK-432. Non-traumatic chylothorax is a rare complication of lung cancer.

Simultaneous bilateral spontaneous pneumothorax observed during the administration of gefitinib for lung adenocarcinoma with multiple lung metastases.

A 41-year-old man with productive cough was admitted to our hospital. His chest roentgenogram showed multiple small nodules in the bilateral lung fields. The nodules were revealed as intrapulmonary metastases of the adenocarcinoma of the lung. Systemic chemotherapy with paclitaxel and carboplatin was not effective, and continuous oral gefitinib therapy was initiated. Twenty-one days later, spontaneous pneumothorax was found in the left lung, and four days after that, in the right lung as well. The extent of the pneumothorax was slight; therefore, he recovered without drainage within several days. Spontaneous pneumothorax, especially bilateral pneumothorax, is a rare complication of chemotherapy for lung cancer.

[A case of lung cancer with cranial neuropathy as the first sign of onset due to metastatic leptomeningeal carcinomatosis].

A 68-year-old man suffered right facial palsy and left deafness, however, his condition was considered to be idiopathic and he was followed. Three months later, bloody sputum and hoarseness caused him to be admitted to our hospital. An abnormal shadow was detected in the right upper lung field and adenocarcinoma of the lung with multiple brain metastases was diagnosed. He underwent gamma-knife radiosurgery for the brain lesions and subsequent systemic chemotherapy consisting of combined carboplatin and paclitaxel, which were not effective. Subsequently various neurological symptoms appeared, such as muscle weakness of the extremities, dizziness, and gait disturbance. Adenocarcinoma cells confirmed in the cerebrospinal fluid were similar to those in the obtained by transbronchial curetting. Whole-brain irradiation was performed, however, the neurological symptoms worsened and he died. Leptomeningeal carcinomatosis is difficult to diagnose while the patient is alive. It is thought that cranial neuropathy due to leptomeningeal carcinomatosis is a rare form of onset for lung cancer.

Nuclear survivin expression in small cell lung cancer.

BACKGROUND/AIM: Little evidence exists regarding a relationship between survivin expression and prognosis in small cell lung cancer (SCLC). We investigated the relationship between survivin expression, clinical characteristics and prognosis in SCLC patients. MATERIALS AND METHODS: We retrospectively reviewed medical records of study patients and analyzed their tumor sections using nuclear survivin labeling index (LI). RESULTS: A significant correlation between nuclear survivin LI and clinical stage was found (p=0.012). In multivariate analysis, a significant association was found between survival and clinical stage (hazard ratio (HR)=2.09; 95 % confidence interval (CI)=1.08-4.31; p=0.027) but not between survival and nuclear survivin LI (HR=0.96; 95 % CI=0.91-1.02; p=0.2). CONCLUSION: We did not find any positive relationship between nuclear survivin expression and survival in SCLC patients. Conversely, we found a positive relationship between clinical stage and nuclear survivin LI, which is considered to be useful in deciding treatment strategies.

Gefitinib in patients with brain metastases from non-small-cell lung cancer: review of 15 clinical cases.

The clinical efficacy of gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), on brain metastases (BMs) from non-small-cell lung cancer (NSCLC) was evaluated. Fifteen patients with recurrent NSCLC with metastasis to the brain were treated with gefitinib. The objective tumor response rate (60%; 9 of 15 patients) for BM was the same as for primary tumors. The median time to response of BM was 26 days. In 8 of 9 patients who exhibited partial response in the thoracic lesion, BM showed dramatic regression, including 1 complete response. One patient with stable primary tumor also exhibited partial response in BM with this monotherapy. Brain metastasis-related neurologic symptoms such as hemiparesis, dysarthria, dysphagia, and vertigo improved or disappeared with the objective response of BM as confirmed by magnetic resonance imaging. Central nervous system toxicities were not observed during the treatment. Four of the 9 BM responders are still under treatment with neither adverse events nor disease progression. Two discontinued the treatment because of severe hepatic toxicity and 3 died because of acquired resistance in pulmonary lesions, even though partial response was observed in the BMs. Finally, median duration of response of BM was 8.7 months and median overall survival was 8.3 months (range, 1.8 to > 15.7 months). Molecular targeted therapy against EGFR could be an option for the treatment of BM from NSCLC refractory to conventional chemotherapy plus radiation therapy because it has demonstrated a distinct therapeutic potential against BM compared with primary lung tumor and extracranial metastases.

Treatment of Non-Small-Cell Lung Cancer with Erlotinib following Gefitinib-Induced Hepatotoxicity: Review of 8 Clinical Cases.

Objective. Gefitinib often induces liver damage. A few reports have described that the subsequent administration of erlotinib was associated with less hepatotoxicity, but the safety and efficacy of this treatment are still not fully investigated. Therefore, we evaluated retrospectively the patients with erlotinib following gefitinib-induced hepatotoxicity. Methods and Patients. We retrospectively reviewed the medical records between December 2007 and March 2010. The patients were evaluated including the following information: age, gender, histology of lung cancer, performance status, smoking status, epidermal growth factor receptor (EGFR) mutation status, liver metastasis, viral hepatitis, alcoholic liver injury, clinical response, and hepatotoxicity due to EGFR tyrosine kinase inhibitors. Results. We identified 8 patients with erlotinib following gefitinib-induced hepatotoxicity. All achieved disease control by gefitinib. Hepatotoxicity was grades 2 and 3 in 3 and 5 patients, respectively. The median duration of treatment with gefitinib was 112.5 days and the median time to gefitinib-induced hepatotoxicity was 51.5 days. The median duration of treatment with erlotinib was 171.5 days. Grade 1 and 2 erlotinib-induced hepatotoxicity was observed in 2 and 1 patient, respectively. Conclusions. Erlotinib administration with careful monitoring is thought to be a good alternative strategy for patients who respond well to gefitinib treatment but experience hepatotoxicity.