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)

Despite improvements in conventional treatment, patients with advanced non-small-cell lung cancer (NSCLC) have a poor prognosis, leaving a significant unmet need for novel treatments. One such novel, biologically targeted agent is the orally active epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. This open-label pilot trial investigated the safety, pharmacokinetics, and efficacy of 2 doses of gefitinib (250 and 500 mg per day) combined with docetaxel (75 mg/m2) in patients with locally advanced or metastatic NSCLC as first- and second-line chemotherapy. Eighteen patients were recruited: 6 received gefitinib 250 mg per day plus docetaxel; 12 received gefitinib 500 mg per day plus docetaxel. Combination therapy was feasible with no overlapping toxicities. No patients experienced dose-limiting toxicities (DLTs) at 250 mg per day; 1 patient had 2 DLT events at 500 mg per day (grade 3 rash and diarrhea for >4 days). Adverse events were mild to moderate, including fatigue, mucositis, nausea, anorexia, rash, diarrhea, and fever. Docetaxel did not appear to alter steady-state exposure to gefitinib. The effect of gefitinib on exposure to docetaxel was equivocal; with the exception of 2 patients in the gefitinib 250 mg per day dose group, there appeared to be no trend toward a higher or lower exposure to docetaxel when given in the presence of gefitinib compared with that when given alone. Combination therapy was associated with antitumor activity and responses were seen with gefitinib in 2 of 6 patients at 250 mg per day and 4 of 12 patients at 500 mg per day. This combination is feasible and has an acceptable and predictable safety profile, as well as associated antitumor activity.
Clin Lung Cancer 2005 May
PMID:A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer. 1594 94

Exisulind is a sulfone derivative of sulindac that induces apoptosis and demonstrates synergy with docetaxel in lung cancer models. This study evaluated the safety, efficacy, and pharmacokinetic interactions of exisulind and docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer (NSCLC). Fifty-seven patients received 218 cycles of docetaxel (75 mg/m2) and carboplatin (area under the curve, 5.0) in combination with exisulind (125-250 mg orally twice daily). Two complete responses and 9 partial responses were observed among the 47 patients assessable for response (overall response rate, 23%). The median duration of response was 5.9 months and median survival was 9.4 months. The 1- and 2-year survival rates are 35% and 14%, respectively. The hematologic toxicities were consistent with those previously reported with docetaxel/carboplatin. The most common nonhematologic toxicities were mild to moderate fatigue, anorexia, nausea, and vomiting. The addition of exisulind to the chemotherapy regimen did not interfere with the metabolism or elimination of docetaxel and vice versa, and docetaxel did not interfere with the pharmacokinetic parameters of exisulind. This trial did not allow direct comparison of patients receiving docetaxel/carboplatin with and without exisulind, but when compared with historical data of docetaxel/carboplatin alone, the addition of exisulind does not appear to enhance antitumor activity, duration of response, or survival. Although preclinical data demonstrate increased apoptosis and prolonged survival for the combination of exisulind and docetaxel, multiple clinical trials do not support further clinical development of this combination regimen in patients with advanced NSCLC.
Clin Lung Cancer 2005 May
PMID:A phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer. 1594 97

To identify differences in the clinical, radiologic, and microbiologic features of pulmonary tuberculosis (TB) in the young (<64 yr) and elderly (> or =65 yr), we performed a retrospective analysis of the medical charts and chest radiographs of 207 young and 119 elderly pulmonary TB patients. Hemoptysis and a febrile sense were more frequent in the young, whereas weakness, dyspnea, anorexia, and mental change were more frequent in the elderly. Elderly patients showed higher frequencies of cardiovascular and chronic lung diseases, whereas the young showed a higher proportion of underlying liver disease. In addition, chest radiography showed a significantly higher frequency of mid or lower lung involvement by TB lesions in the elderly (10.6% vs. 22.7%, p<0.05). Lesions were frequently misdiagnosed as pneumonia or lung cancer in the elderly. However, there was no difference between these two groups in terms of sputum acid-fast bacilli positivity. The elderly showed a higher frequency of adverse drug reactions (18.5% vs. 40.7%, p<0.05), and higher TB-related mortality (1.3% vs. 11.1%, p<0.05). In conclusion this study showed that young and elderly pulmonary TB patients have similar microbiologic features; however, the elderly showed higher frequencies of atypical clinical and radiologic presentations, adverse drug reactions, and higher TB-related mortality.
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PMID:Diagnostic and therapeutic problems of pulmonary tuberculosis in elderly patients. 1622 52

Although we have made steady improvements in the survival rates of patients with advanced-stage lung cancer, the majority of patients still experience distress and suffering. Although the symptom burden is greatest in patients in the end stages of life, many patients living with lung cancer suffer from troubling symptoms and side effects of therapy. Even long-term survivors with early-stage non-small-cell lung cancer (NSCLC) often experience respiratory symptoms, such as dyspnea and cough. Because of the high prevalence of NSCLC and the frequency with which it presents in an incurable stage, symptom management is a large component of the care of these patients. Dyspnea, cough, fatigue, anorexia/cachexia, and pain are the most common symptoms in patients with advanced-stage NSCLC. Cancer-directed therapy can improve some of these symptoms but often incompletely and temporarily. Therefore, comprehensive care of patients with advanced-stage NSCLC must include therapies targeted at these difficult and distressing symptoms.
Clin Lung Cancer 2006 Jan
PMID:Comprehensive symptom management in patients with advanced-stage non-small-cell lung cancer. 1651 77

Symptoms such as cough and hemoptysis in patients with lung cancer can be the consequence of local bronchopulmonary disease, tumor growth that leads to compression of surrounding structures, distant metastases, diverse systemic effects (anorexia, asthenia, weight loss), or paraneoplastic syndromes associated with tumor production of certain hormones. Approximately 10% of patients are asymptomatic at diagnosis. We report the case of a 77-year-old man with dyspnea, pleuritic chest pain, and lower limb edema. The patient died within a few days. The cause of the clinical picture was constrictive pericarditis secondary to metastases from lung carcinoma.
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PMID:[Constrictive pericarditis as the first sign of lung cancer]. 1712 98

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.
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PMID:Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. 1713 66

Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.
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PMID:[VEGF in the cancer anorexia-cachexia syndrome in patients with lung cancer]. 1726 67

We present our experience with skeletal involvement of Pneumocystis jiroveci (ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.
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PMID:Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient. 1733 Dec 92

Vitamin A deficiency has been commonly observed in patients with tuberculosis. Low serum retinol levels return to normal after antituberculosis treatment even when no supplements are provided. The deficiency of vitamin A observed in patients with tuberculosis might have contributed to the development of tuberculous disease in them. Alternatively, deficiency could be the result of loss of appetite, poor intestinal absorption, increased urinary loss of vitamin A or acute phase reaction in TB. Vitamin A deficiency lowers immunity while vitamin A supplementation reduces morbidity and mortality, particularly from measles and diarrhoea. Vitamin A supplementation also decreases the mortality rate in HIV-infected children and delays the progression of HIV disease in infected subjects. A higher incidence of lung cancer and increased mortality have been observed in smokers after beta-carotene supplementation. Zinc deficiency is also common in tuberculosis, which may impose a secondary vitamin A deficiency. Clinical trials have shown conflicting results regarding the effect of supplementation of vitamin A, alone or with other micronutrients, on time taken to sputum conversion in patients with pulmonary tuberculosis. Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in patients with tuberculosis, but clinical trials on such a combination are lacking.
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PMID:Role of vitamin A supplementation in the treatment of tuberculosis. 1755 17

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others. Eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil can help in the management of persistent chronic inflammatory states, but treatment's compliance is generally poor. Preferentially, Cox-2 inhibition can create a favorable pattern of cytokines by decreasing the production of certain eicosanoids, although their role in SIMS is unknown. The aim of this study was to test the hypothesis that by modulating systemic inflammation through an eicosanoid-targeted approach, some of the symptoms of the SIMS could be controlled. We exclusively evaluated 12 patients for compliance. Patients were assigned 1 of the 4 treatment groups (15-, 12-, 9-, or 6-g dose, fractionated every 8 h). For patients assigned to 15 and 12 doses, the overall compliance was very poor and unsatisfactory for patients receiving the 9-g dose. The maximum tolerable dose was calculated to be around 2 capsules tid (6 g of fish oil per day). A second cohort of 22 patients with advanced lung cancer and SIMS were randomly assigned to receive either fish oil, 2 g tid, plus placebo capsules bid (n = 12) or fish oil, 2 g tid, plus celecoxib 200 mg bid (n = 10). All patients in both groups received oral food supplementation. After 6 wk of treatment, patients receiving fish oil + placebo or fish oil + celecoxib showed significantly more appetite, less fatigue, and lower C-reactive protein (C-RP) values than their respective baselines values (P < 0.02 for all the comparisons). Additionally, patients in the fish oil + celecoxib group also improved their body weight and muscle strength compared to baseline values (P < 0.02 for all the comparisons). Comparing both groups, patients receiving fish oil + celecoxib showed significantly lower C-RP levels (P = 0.005, t-test), higher muscle strength (P = 0.002, t-test) and body weight (P = 0.05, t-test) than patients receiving fish oil + placebo. The addition of celecoxib improved the control of the acute phase protein response, total body weight, and muscle strength. Additionally, the consistent nutritional support used in our patients could have helped to maximize the pharmacological effects of fish oil and/or celecoxib. This study shows that by modulating the eicosanoid metabolism using a combination of n-3 fatty acids and cyclooxygenase-2 inhibitor, some of the signs and symptoms associated with a SIMS could be ameliorated.
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PMID:Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. 1792 97


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