Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung cancer is one of the most common cancers and its associated mortality continues to rise in Japan. The lung cancer cure rate is still very low. To improve the survival of patients with lung cancer, well-designed and well-conducted clinical trials are essential. Several Japanese study groups have been conducting clinical trials for lung cancer. However, most randomized phase III studies were conducted by the Japan Clinical Oncology Group (JCOG), the West Japan Thoracic Oncology Group, and pharmaceutical companies supporting temporarily organized groups. In the past decade, the quality of Japanese clinical studies has improved tremendously. The results of JCOG9511 have recently been reported; and demonstrated that treatment with irinotecan/cisplatin significantly improved patient survival in extensive-stage small-cell lung cancer over standard etoposide/cisplatin, with less myelosuppression. A randomized phase II study using gefitinib (ZD1839; Iressa) for non-small-cell lung cancer was also recently reported and showed a high response rate against platinum-refractory lung cancer, especially in adenocarcinoma and in females. A 4-arm multicenter, randomized cooperative phase III study for advanced non-small-cell lung cancer is currently underway.
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PMID:Results of recent Japanese clinical trials in lung cancer. 1466 31

Gefitinib (Iressatrade mark) is an epidermal growth factor receptor tyrosine kinase inhibitor that has been approved for the treatment of lung cancer in Japan, however, after marketing several cases of severe pulmonary toxicity were reported. The West Japan Thoracic Oncology Group conducted an independent survey of acute pulmonary toxicity and interstitial lung disease (ILD) caused by gefitinib in its member's institutions. The purpose of this study was to clarify the image characteristics of ILD caused by the molecular-targeting drug gefitinib. A total of 1976 patients had been treated with gefitinib between August and December 2002, and 102 of them were suspected of having acute pulmonary toxicity and ILD. A final definite diagnosis of gefitinib-induced ILD was made by at least three radiologists based on a review and analysis of the chest radiography and CT findings plus the clinical data in the medical records. The imaging findings were classified into four patterns: (A) a nonspecific area with ground-glass attenuation, (B) a multifocal area of airspace consolidations, (C) patchy distribution of ground-glass attenuation accompanied by interlobar septal thickening, and (D) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. CT as well as chest radiography had been performed in 65 of the 102 patients at the onset of ILD, and chest radiography alone had been performed in 26. After excluding 11 cases with insufficient data and 21 cases concluded to be other pulmonary diseases, 70 patients were diagnosed with gefitinib-induced ILD. Finally, the diagnostic image findings were classified as pattern A in 29 cases, pattern B in 7 cases, pattern C in 3 cases, pattern D in 20 cases and others in 11 cases. The CT images were classified as pattern A, B, C, and D in 24, 7, 1, and 12 cases, respectively. The mortality rate was significantly higher in the patients with pattern D than the other patterns. Pattern D were thought to represent the features of diffuse alveolar damage. In conclusion, the molecular-targeting drug gefitinib induces pulmonary toxicity at a certain rate and the imaging findings of ILD induced by gefitinib are similar to those of pulmonary toxicity induced by conventional antineoplastic agents.
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PMID:Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group. 1657 71

Clinical studies have demonstrated that gefitinib, an epidermal growth factor receptor inhibitor, is an effective treatment for some patients with advanced non-small cell lung cancer and is generally well-tolerated. However, several reports have also suggested that gefitinib is associated with acute lung injury and subsequent fibrosis. One hypothesis is that gefitinib exacerbates lung injury induced by radiation therapy. It is important to confirm the safety of gefitinib in radiotherapy for patients with lung cancer. In this preclinical study we aimed to clarify the effect of gefitinib on thoracic radiotherapy. Six-week-old female C57BL/6 mice were immobilized in a plastic frame, and the thorax was irradiated once with a dose of 12 Gy on day 0. Gefitinib (20, 90 and 200 mg/kg/day) was administered on days 0 to 5 (acute phase) or days 14 to 19 (late phase) postirradiation. Thoracic irradiation induced lung injury and subsequent fibrosis 5 months later. Gefitinib, administered in the acute phase, had no effect on lung fibrosis or collagen levels induced by irradiation. A high dose of gefitinib (200 mg/kg/day) administered during the late phase significantly reduced fibrosis scores and collagen levels. These results suggest that gefitinib does not exacerbate radiation-induced lung injury and fibrosis in this strain of mice. Therefore, thoracic irradiation is unlikely to be a risk factor for lung injury associated with gefitinib treatment.
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PMID:Effects of gefitinib on radiation-induced lung injury in mice. 1847 30