Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification of the human epidermal growth factor receptor 2 protein (HER2) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients. Trastuzumab (Herceptin, Genentech, Inc., South San Francisco, California) is a highly purified recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that binds with high affinity and specificity to the extracellular domain of the HER2 receptor. In vitro and in vivo preclinical studies have shown that administration of trastuzumab alone or in combination with paclitaxel or carboplatin significantly inhibits the growth of breast tumor-derived cell lines that overexpress the HER2 gene product. At therapeutic doses in breast cancer patients, the mean half-life of trastuzumab is 5.8 days. Trastuzumab serum concentrations reach steady state with mean trough and peak concentrations of 79 microg/mL and 123 microg/mL, respectively. In a 222-patient, single-arm clinical study, treatment with a loading dose of trastuzumab 4 mg/kg administered IV followed by weekly IV doses of 2 mg/kg produced an overall response rate of 14% (2% complete remission and 12% partial remission). The beneficial effects were greatest in patients with the greatest degree (3+) of HER2 protein overexpression. In another clinical study, 469 women with metastatic breast carcinoma were randomized to a paclitaxel or anthracycline-plus-cyclophosphamide regimen with or without trastuzumab. The overall response rate was significantly greater in the trastuzumab-plus-chemotherapy group than in the chemotherapy-alone cohort. The magnitude of observed effects was greatest with pacli taxel plus trastuzumab. The most common adverse effects attributed to trastuzumab in clinical studies were fever and chills, pain, asthenia, nausea, vomiting, increased cough, diarrhea, headache, dyspnea, infection, rhinitis, and insomnia. Trastuzumab in combination with chemotherapy can lead to cardiotoxicity, leukopenia, anemia, diarrhea, abdominal pain, and infection. Trastuzumab has been approved by the US Food and Drug Administration as a single agent for the treatment of patients who have metastatic breast cancer involving overexpression of the HER2 protein and who have received 1 or more chemotherapy regimens; in combination with paclitaxel, it has been approved for the treatment of such patients who have not received chemotherapy.
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PMID:Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. 1021 34

The majority of patients with non-small cell lung cancer (NSCLC) present with advanced disease, which is associated with a poor prognosis and symptoms such as pain, coughing, and shortness of breath. In patients who present at an earlier stage, the progressive nature of NSCLC and its resistance to treatment often result in recurrence, with the associated symptoms of advanced disease. These symptoms negatively affect patient quality of life and performance status rating, both of which are predictive of treatment response and survival. There is increasing interest in using assessments of improvements in symptoms and quality of life as outcomes in clinical trials for patients with advanced NSCLC. Patients with NSCLC have limited therapeutic options. Even those patients who are able to tolerate chemotherapy can expect median survival increases of only 2 to 4 months. The new targeted therapies for lung cancer, in contrast, are relatively nontoxic and may provide benefits for symptoms and quality of life in addition to tumor responses. The Functional Assessment of Cancer Therapy-Lung (FACT-L) scale is a validated, sensitive, and reliable patient questionnaire that evaluates and quantifies quality of life across several dimensions, including lung cancer-related symptoms (Lung Cancer Subscale). The Lung Cancer Subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). A change of two points reflects a clinically significant change in NSCLC-related symptoms and quality of life. In phase I studies and also in the Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL)-1 and IDEAL-2 phase II monotherapy trials, treatment of patients with advanced NSCLC with the epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca Pharmaceuticals LP, Wilmington, DE) has shown tumor responses as well as rapid improvements in NSCLC-related symptoms and quality of life. In IDEAL-1 and IDEAL-2, improvements in NSCLC-related symptoms and quality of life, as measured by FACT-L, correlated with tumor response, and improvements in symptoms also correlated with progression-free and overall survival. Although symptom response is correlated with tumor response, it is also uniquely predictive of progression-free and overall survival. The FACT-L questionnaire has also been included in phase III trials of ZD1839 treatment in combination with chemotherapy regimens.
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PMID:Impact of ZD1839 on non-small cell lung cancer-related symptoms as measured by the functional assessment of cancer therapy-lung scale. 1264 83

Gefitinib is a newly developed molecular-target drug with selective inhibitory activity for tyrosine kinase of the epidermal growth factor receptor and has an encouraging effect on non-small cell lung cancer in an advanced stage. The adverse drug reactions including diarrhea, skin eruptions and liver dysfunction have been considered mild. However, cases of severe acute lung injuries were reported after approval of the drug in Japan in July, 2002. We report a case of recurrent large cell carcinoma of the lung in a 73-year-old man who suffered from radiation recall pneumonitis induced by Gefitinib. Two months after radiation therapy to the mediastinal and right hilar lesions was completed, he started to take Gefitinib at a dose of 250 mg/day. Six weeks later, he complained acutely of a dry cough, slight fever and effort dyspnea, and his chest CT demonstrated ground-glass opacity corresponding to the previous radiation field. In administering Gefitinib, as well as other cytotoxic drugs, meticulous monitoring for acute lung injury and radiation recall reaction is required.
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PMID:[Radiation recall pneumonitis induced by Gefitinib (Iressa): a case report]. 1450 45

The epithelial cells lining the airways serve protective functions. The "barrier function" of the epithelium protects the individual from damage by inhaled irritants. The epithelium produces mucins which become hydrated and form a viscoelastic gel which spreads over the epithelial surface. In healthy individuals inhaled foreign materials become entrapped in the mucus and are cleared by mucociliary transport and by coughing. In many chronic inflammatory airway diseases, however, excessive mucus is produced and is inadequately cleared, leading to mucous obstruction and infection. At present there is no specific treatment for hypersecretion. However, the discovery that an epidermal growth factor receptor (EGFR) cascade is involved in mucin production by a wide variety of stimuli suggests that blockade may provide specific treatment for hypersecretory diseases. EGFR pathways have also been implicated in the repair of damaged airway epithelium. The roles of EGFR in airway epithelial cell hypersecretion and epithelial damage and repair are reviewed and future potential treatments are suggested.
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PMID:Roles of epidermal growth factor receptor activation in epithelial cell repair and mucin production in airway epithelium. 1551 78

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

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.
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PMID:Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. 1594 98

Erlotinib (Tarceva, OSI-774; Pfizer, Inc.) is an orally-active, targeted inhibitor of the epidermal growth factor receptor (EGFR/HER1), which is part of a key regulatory pathway in cancer. Patients with advanced, incurable non-small cell lung cancer (NSCLC) may derive a clinical benefit from first- and second-line chemotherapy, but third-line treatment with available cytotoxic agents is not effective. Remarkably, EGFR/HER1 antagonists have demonstrated activity as second- and even third-line treatment for this disease. Erlotinib is the first of this novel class of drug to demonstrate a statistically significant and clinically relevant difference in overall survival, progression free survival and time to disease related symptoms (cough, pain, shortness of breath) compared with treatment with best supportive care in patients who have failed standard first- or second-line chemotherapy. This paper reviews the pharmacology, preclinical and clinical data to support the use of erlotinib in NSCLC.
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PMID:Erlotinib in non-small cell lung cancer: a review. 1595 27

Hypertrophic osteoarthropathy is an important manifestation of lung carcinoma, particularly in a non-small cell tumor, and hampers quality of life. Although removal of the primary tumor usually resolves this syndrome, effective treatment in patients with advanced lung carcinoma has not been established. Recently, an orally active, selective epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor ("Gefitinib") provided clinical anti-tumor activity. We describe a 71-year-old male smoker with cough, who presented with clubbed fingers. A transbronchial lung biopsy (stage T2N3M1-IV) on a cavity lesion in the left lower lobe showed the features of adenocarcinoma, while bone scintigram revealed bilaterally symmetrical abnormal uptakes in the lower extremities, suggesting secondary hypertrophic osteoarthropathy. The serum level of growth hormone was increased to 1.42 ng/ml. Chemotherapy (cisplatin, vinorelbine) was not effective. Gefitinib, as a second-line therapy, induced disappearance of the abnormal accumulation on bone scintigraphy and decrease of the cavity in the lung and of serum growth hormone. The presented case suggests that the EGFR inhibitor might be a promising option for the treatment of hypertrophic osteoarthropathy with advanced lung adenocarcinoma.
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PMID:Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma. 1608 Apr 71

15 cases of pulmonary neuroendocrine cell hyperplasia (carcinoid-tumorlets, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/DIPNECH) and 20 neuroendocrine pulmonary tumors (10 carcinoid tumors, 5 large cell neuroendocrine, and 5 small cell neuroendocrine lung carcinomas) were immunohistochemically analyzed for the expression of epidermal growth factor receptor (EGFR, = HER-1). All cases of neuroendocrine cell hyperplasia exhibited a maximum EGFR expression (score 3 in 100% of cells) showing predominantly membranous, partly cytoplasmic staining. 4 ot the 10 carcinoid tumors were strongly positive for EGFR, whereas the other 6 were EGFR-negative. A total of 90% of large cell neuroendocrine and small cell neuroendocrine carcinomas were negative for EGFR. Overexpression of EGFR in pulmonary neuroendocrine cell hyperplasia might be significant for the pathogenesis of these lesions. As DIPNECH is characterized by clinical signs and symptoms including mild cough and obstructive functional impairment, a specific antagonistic therapeutic trial could aim at blocking EGFR/HER-1 or its subsequent signal transduction pathway.
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PMID:[EGFR-expression in pulmonary neuroendocrine cell hyperplasia]. 1643 94

A 47-year-old woman who had never smoked was evaluated for chest wall pain, cough and dyspnea that proved to be due to neoplastic right pleural disease with effusion. Cytological examination of the pleural fluid and histological analysis of a biopsy specimen of the pleural mass obtained during thoracoscopy were consistent with a diagnosis of small cell carcinoma. The patient was treated with two lines of chemotherapy and with octreotide, but without any clinical or radiological benefit. Since there was immunohistochemical overexpression of epidermal growth factor receptor, the patient was treated with gefitinib. Despite an initial clinical improvement she died due to disease progression. This case of a refractory pleural small cell carcinoma, which is an extremely rare disease, is the first reported in a never smoker and the first to be fully characterized for EGFR status.
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PMID:Refractory pleural small cell carcinoma in never smoker. A case report. 1870 17


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