Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibreoptic bronchoscopy (FOB) helps in visualisation of the endobronchial tree. Fibreoptic bronchoscopies were done in 429 cases between January 1999 and January 2000 [322 men (75.1%) and 107 women (24.9%)]. Patients were between 12 and 89 years of age (mean+/- SD = 49 +/- 15.1 years). Of which, 196 (45.7%) had lung cancer and 233 (54.4%) had non-malignant disease [Tuberculosis (TB) 26, miliary TB 16, non-resolving pneumonia 29, atypical pneumonia 10, bronchiectasis 11, aspergillosis 12, sarcoidosis 17, interstitial lung disease (ILD) 20, haemoptysis with normal chest x-ray 13 and miscellaneous 79]. In this series of 429 patients a significant number of patients (n = 127) presented with fever (38 malignant and 89 non-malignant disease, p < 0.0001), 137 had haemoptysis (74 malignant and 63 non-malignant disease, p < 0.01), 89 had chest pain (61 malignant and 28 non-malignant disease, p < 0.0001) and 29 patients presented with complaint of anorexia (21 malignant and 8 non-malignant disease, p < 0.003). High prevalence of lung lesions in the right upper lobe [10.4% (43 of 411)] and left main bronchus [12% (49 of 411)] was observed. Left upper lobe showed 8.7% (36 patients) lesions and right middle lobe showed 5.5% (23 patients) lesions. In 143 (34.8%) patients, FOB findings were normal. Out of 407 patients, FOB was suggestive of necrotic/nodular growth in 159 patients (39.1%), infiltrative growth in 8 patients (1.9%), and extrinsic compression was found in 39 patients (9.6%). In 143 patients (35.2%) no endobronchial growth was seen. Bronchial biopsy (BB) was performed in 162 (37.8%) patients, transbronchial lung biopsy in 56 patients (13.1%), bronchial washing for cytology in 350 patients (81.5%), bronchial washing for AFB in 302 patients (70.3%), bronchial washing for culture in 67 patients (15.6%), bronchial washing for fungus in 64 patients (14.9%) and Pneumocystis carinii infection was looked for in 6 patients (1.4%). Postbronchoscopy complications were recorded as follows: Early termination of FOB due to decreased O2 saturation in 10 cases (2.4%), postbiopsy bleeding in 5 cases (1.2%), post FOB fever in 5 cases (1.2%), chest pain in 7 patients (1.7%) and pneumothorax occurred in 2 patients (0.5%). FOB performed in outpatient setting is a useful and safe modality. Most patients in whom FOB was done in the present setup had suspected lung cancer. No major complications were encountered.
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PMID:Bronchoscopy in adults at a tertiary care centre: indications and complications. 1547 75

Gefitinib is a small molecule that specifically inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) type 1 by interfering with the adenosine triphosphate (ATP) binding site. At doses that maximally inhibit EGFR tyrosine kinase activity chosen for phase II trials, the most common side effects of gefitinib are low-grade rash or diarrhea. An infrequent but serious side effect of gefitinib is interstitial lung disease (ILD). The Iressa dose evaluation for advanced lung cancer phase II trials (IDEAL 1 and IDEAL 2) of single agent gefitinib, 250 or 500 mg orally per day in pretreated patients with non-small cell lung cancer (NSCLC), found about 20% of patients on IDEAL-1 and 10% of patients on IDEAL-2 had major objective responses and improvement of symptoms. The data from the IDEAL trials and the extensive experience from the 21,000 patients treated on the expanded access program, suggests that the patients who have a major objective response probably have a significant survival benefit in addition to palliative benefit. In addition, approximately 40% of patients on the IDEAL trials experienced improvement in symptoms. Gefitinib was approved for third line treatment of NSCLC. Gefitinib is effective, safe, and well-tolerated single-agent therapy in previously treated NSCLC. Although there have been no direct comparisons, the small molecule inhibitors of EGFR gefitinib and erlotinib appear to have similar efficacy. Erlotinib has been shown to produce a survival advantage compared to best supportive care in an unselected group of previously treated patients with NSCLC. Until similar trials are completed comparing gefitinib to best supportive care, there is a similar survival advantage for gefitinib. Nonsmokers, women, and patients with adenocarcinoma, are more likely to have major objective responses than other patients. Bronchioalveolar lung cancer is a subtype of NSCLC that is more likely to respond to gefitinib. Several groups have now reported that most, but not all, tumors experiencing a major objective response to gefitinib have mutations associated with the ATP-binding site of EGFR. It is reasonable to move gefitinib in to second-line therapy for patients who are known to have a tumor that is more likely to respond to gefitinib. Also, I would treat such patients with gefitinib as first-line therapy on an appropriate clinical trial approved by the Institutional Review Board (IRB). Outside of a clinical trial, patients with advanced disease should initially be treated with a combination of doublet chemotherapy. There is strong evidence that there is no benefit to concurrent chemotherapy and gefitinib. Gefitinib should not be given concurrently with cytotoxic chemotherapy as initial treatment for NSCLC. Sequential therapy combining chemotherapy and gefitinib in advanced disease or as adjuvant therapy should only be done in the context of a clinical trial approved by the IRB. There is preclinical evidence suggesting that gefitinib is a radiosensitizer. Early results from trials combining radiation, or chemoradiotherapy with gefitinib have shown that these combinations are without excessive additive toxicity. There is no proven clinical benefit for concurrent Gefitinib and radiation. Gefitinib should only be given with radiation as part of an appropriate clinical trial approved by the IRB.
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PMID:Gefitinib therapy for non-small cell lung cancer. 1561 Jul 17

Lung cancer often develops in individuals with pre-existing pulmonary and cardiac pathology. Many of these individuals with pre-existing pathology are also at risk of occupational lung disease. New and worsening symptoms can be secondary to pre-existing pathology, progressive cancer or treatment. Pulmonary toxicity, including interstitial lung disease, following radiotherapy and conventional cytotoxic chemotherapy (e.g. cyclophosphamide, bleomycin), has been recognised for many years. Pulmonary toxicity also occurs with the newer classes of cytotoxic agents, including the deoxycytidine analogue gemcitabine. A small percentage (0.88%) of patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib have developed interstitial lung disease. This complication has been reported at a higher frequency in Japanese patients than in US patients (1.9% vs 0.34%, respectively) and in those with pre-existing pulmonary fibrosis. This review discusses the difficulties in both recognition and treatment of gefitinib-associated interstitial lung disease. Symptoms are vague, such as dyspnoea, cough and fever and can be difficult to differentiate from progressive disease, co-existing morbidity and new pulmonary pathology. Diagnosis is, therefore, by rigorous investigation to exclude all other differential diagnoses. Treatment, at present, is supportive and includes discontinuation of gefitinib, oxygen supplementation, high-dose corticosteroids and antibacterials.
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PMID:Interstitial lung disease in lung cancer: separating disease progression from treatment effects. 1569 Dec 21

Although pulmonary toxicity associated with gefitinib, an epidermal growth factor receptor inhibitor, has been reported recently, the accumulation of clinical information and the underlying mechanisms of gefitinib-induced interstitial lung disease (ILD) remain insufficient and unclear. After retrospectively reviewing the clinical records and chest X-rays of 489 lung cancer patients who were treated with gefitinib, we diagnosed four cases of gefitinib-induced ILD who underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). We found that the period of time from starting gefitinib to the onset of ILD was short, and concluded that a careful and close observation of a chest imaging study and a collection of respiratory symptoms was recommended. All four patients were treated with a high dose of corticosteroids, and ILD was resolved. We detected high levels of interferon-inducible protein-10 in BAL fluid, although we could not demonstrate the characteristic features of laboratory findings or BAL fluid cell analysis. We speculated that a Th1 type of lung tissue inflammation or lung injury might be involved as a part of mechanisms underlying gefitinib-induced ILD.
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PMID:Interstitial lung disease associated with gefitinib. 1613 74

Gefitinib (Iressa, ZD 1839) is an orally bioavailable small molecule that selectively inhibits epidermal growth factor receptor(EGFR) tyrosine kinase activity. Gefitinib causes a dramatic response in approximately 10% to 20% of patients with non-small-cell lung cancer (NSCLC) who receive prior chemotherapy. Studies of gefitinib in combination chemotherapy in first-line therapy of advanced NSCLC have, however, failed to show improvement of survival. Gefitinib also failed to prolong survival in a placebo controlled clinical trial for patients with pretreated advanced NSCLC. In addition, gefitinib did not improve survival as maintenance therapy after chemoradiation in patients with Stage III NSCLC. A possible explanation for the lack of a survival benefit seen in these studies might be failure to select of patients suitable for gefitinib treatment. Empirically, and also in phase II trials, a good clinical response has been observed most frequently in women, nonsmokers, patients with adenocarcinomas, and East Asian patients. Recently, mutations and amplifications of the EGFR gene identified in a subset of NSCLC have been reported to be useful for prediction of enhanced sensitivity to gefitinib. It is also known that some recurrent tumors have a secondary mutation in the EGFR kinase domain, T 790 M, conferring drug resistance. In Japan, a significant number of patients often develop fatal interstitial lung disease after the introduction of gefitinib, although it is, in general, well tolerated. In the future, we must demonstrated benefits of gefitinib treatment in prospective clinical trials by recruiting patients selected on the basis of biological characteristics. It is also important to further elucidate various issues that include other determinants of gefitinib sensitivity, other mechanisms of resistance to gefitinib or mechanisms or predictive factors of interstitial lung disease by close collaboration among clinicians and basic researchers.
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PMID:[Molecular targeted therapy--non-small-cell lung cancer and gefitinib]. 1628 20

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.
Lung Cancer 2006 May
PMID:Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group. 1657 71

Interstitial lung disease (ILD) refers to a diverse range of pulmonary fibrotic disorders and may be hard to accurately diagnose, as distinguishing it from other pulmonary diseases can be difficult. Estimations of the incidence in populations are confounded by the complexity of the different forms of the disorder. In addition, ILD is a comorbid disease of lung cancer and is seen after most forms of chemotherapy and radiotherapy for advanced lung cancer. Incidences of >or=10% have been reported; however, whatever the true incidence, both chemotherapy and radiotherapy enhance the risk of developing ILD. ILD has also been reported with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, including erlotinib (Tarceva, OSI-774) and gefitinib (IRESSA). In a large number of gefitinib-treated patients (n > 185,000) an incidence of approx 1% has been observed (approx 2% in Japan; 0.3% in the rest of the world). Nevertheless, as with other treatments for advanced non-small-cell lung cancer, the clinical benefit outweighs the risk of ILD. In this article, we review the data on ILD with EGFR inhibitors and other common lung cancer treatments.
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PMID:Interstitial lung disease in patients with non-small-cell lung cancer treated with epidermal growth factor receptor inhibitors. 1672 Sep 16

Interstitial lung disease is a rare but serious complication of epidermal growth factor receptor tyrosine kinase inhibitor therapy. Although our understanding of this phenomenon remains incomplete, recently there have been significant insights made into the mechanisms of injury, incidence, risk factors, and its clinical manifestations. Japanese patients appear to be at a higher risk (1.6%-3.5%) than patients in the rest of the world (0.3%), and other risk factors, such as coincident interstitial lung disease, concurrent chemotherapy, previous radiation, preexisting pulmonary fibrosis, and male sex, have been identified. In the majority of cases, the histopathology, the acute and often dramatic clinical presentation, and the radiographic findings resemble acute respiratory distress syndrome. Aside from immediate cessation of the offending agent, the treatment is largely supportive, although corticosteroids appear to be of benefit. The mortality remains high at approximately 30%-50%. We present a review of the incidence, risk factors, clinical manifestations, diagnosis, management, and outcome of this disorder.
Clin Lung Cancer 2006 Dec
PMID:Interstitial lung disease associated with epidermal growth factor receptor tyrosine kinase inhibitor therapy in non-small-cell lung carcinoma. 1723 88

Tobacco is implicated in multisystemic carcinogenesis through more than fifty identified carcinogenic metabolites that produce mutations responsible for alterations in cell cycle, immune response and endocrine regulation. Is one of nine risk factors identified in one third of cancer deaths together with obesity, sedentary, alcohol consumption, sexual promiscuity, drug addiction, and open and closed air contamination. Answering for cardiovascular diseases as the first cause of death in civilized world, tobacco is also pointed as the major factor implicated in the development of COPD (chronic obstructive pulmonary disease), RB-ILD (respiratory bronchiolitis and interstitial lung disease), DIP (desquamative interstitial pneumonia), bronchiolitis and bronchiolocentric interstitial fibrosis, Langerhans cells histiocytosis, eosinophilic pneumonia, sarcoidosis, epidermoid metaplasia in respiratory epithelium and lung cancer. The chronic tobacco induced inflammatory state is the basis for the acquisition of genetic alterations dependent on the tobacco contaminants.
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PMID:[Tobacco and morphology: pulmonary diseases]. 1763 77

Epidermal growth factor receptor (EGFR) gene mutations are frequent in lung cancer of Asian ethnicity, female gender, non-smokers,and of adenocarcinoma histology. About 80% of the patients with EGFR mutations respond to EGFR tyrosine kinase inhibitor (TKI) including gefitinib and erlotinib, while only 10% of those without EGFR mutations do so. Therefore, EGFR mutation is being recognized as one of the most reliable predictive factors in gefitinib treatment. Another important issue in clinical practice is fatal interstitial lung disease (ILD) in patients with gefitinib treatment, especially for Asian patients. A nested case-control study recently conducted in Japan identified some risk factors which cause ILD. About half of the acquired resistance to gefitinib that almost always occurs during the course of gefitinib administration is reportedly caused by secondary mutation at codon 79 0 (T 79 0 M). EGFR-TKIs are not universally effective for lung cancer,but these drugs are effective in patients who have particular characteristics. Therefore, patients who would benefit from gefitinib therapy should be included in clinical trials. Based on this concept, phaseIII clinical trials comparing gefitinib monotherapy with standard platinum-based chemotherapy in lung cancer patients with EGFR mutations are ongoing.
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PMID:[Gefitinib and epidermal growth factor receptor gene mutation]. 1768 96


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