Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019079 (hemoptysis)
 6,129 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC) because current chemotherapy regimens are of limited effectiveness. The role of vascular endothelial growth factor in promoting tumor angiogenesis, in maintaining existing vasculature, and in resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin), a monoclonal antibody directed against vascular endothelial growth factor, has shown promise in treating a number of different cancers. In a recent Phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy significantly increased the time to progression and increased the response rate when compared with chemotherapy alone. This was particularly impressive in the subset of patients with non-squamous histology. Bevacizumab is generally well tolerated and did not appear to increase the incidence or severity of nausea/vomiting, neuropathy and renal toxicity, which are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in Phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) seem to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Present ongoing studies are under way in NSCLC including (a) a Phase II neo-adjuvant study in combination with paclitaxel and carboplatin in patients with stage IB-IIA NSCLC; (b) a Phase I/II study of bevacizumab in combination with the epidermal growth factor receptor tyrosine kinase inhibitor agent, Tarceva, in patients with previously treated NSCLC; and (c) an Eastern Cooperative Group randomized Phase III study of paclitaxel and carboplatin with/without bevacizumab in patients with previously untreated IIIB (malignant pleural effusion) or metastatic NSCLC. These studies will help to establish the role of bevacizumab in NSCLC.
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PMID:Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. 1521 70

Targeted therapies are now more often used in lung cancer. Inhibitors of EGFR and of angiogenesis have demonstrated a certain activity in this disease. Some experimental in vitro or in vivo studies are in favour of combined targeted therapies and radiation. For example, additive or supra-additive effects have been shown when inhibitors of the EGFR tyrosine kinase were given with radiation. In advanced lung cancer, the combination of bevacizumab with chemotherapy was demonstrated to produce better survival outcomes. But a high rate of fatal hemoptysis was reported with this drug, particularly for central and squamous tumors. This could be a limitation for its use in combination with radiation. Drugs with multiple targets are becoming available; their association with radiation seems to be promising.
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PMID:[Targeted therapies and radiotherapy in lung cancer]. 1707 84

A 77-year-old woman presented with hoarseness and hemoptysis. Chest CT scan revealed a mediastinal tumor in the lumen of the left pulmonary artery. A definitive diagnosis could not be made based on mediastinoscopy and thoracotomy. Eight months later, multiple nodular shadows appeared in both lung fields.Video-assisted lung biopsy showed that these nodules were lung metastases of a spindle cell sarcoma. Based on the pathological and radiological findings, a pulmonary artery sarcoma was eventually diagnosed. Interestingly, on immunohistological staining, the tumor cells were diffusely positive for KIT, which is an immunohistochemical marker of gastrointestinal stromal tumors. The patient was treated with imatinib, a KIT tyrosine kinase inhibitor; however, the tumors progressed. The relationship between pulmonary artery sarcoma and KIT requires further study.
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PMID:[Diffuse expression of KIT in a pulmonary artery sarcoma]. 1851 91

Inhibition of angiogenesis now plays a central role in the management of many malignancies. Angiogenesis plays an important role in lung cancer and increasing numbers of antiangiogenesis agents are being investigated in all types of pulmonary malignancies. The monoclonal antibody, bevacizumab, has demonstrated efficacy (improved response rates and overall survival) in phase II and III trials in combination with standard first-line chemotherapy in non-small cell lung cancer. However patients in the large phase III studies were highly selected to reduce the risk of fatal hemoptysis. Many small molecule tyrosine kinase inhibitors, particularly sorafenib, sunitinib, vandetanib, and cediranib, are currently being investigated in phase III trials as monotherapy or in combination with standard therapy. Alternative antiangiogenesis approaches such as vascular endothelial growth factor-trap and anticoagulation are also being investigated. Targeting angiogenesis is an exciting and attractive area in the treatment of lung cancer, and the results of ongoing trials are eagerly awaited. More work is required to identify subgroups of patients most likely to benefit from these drugs.
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PMID:Targeting angiogenesis in the treatment of lung cancer. 1882 16

Lung cancer remains the leading cause of cancer mortality in the United States, and the majority of patients will have non-small cell lung cancer (NSCLC) and will present with locally advanced or metastatic disease. In the United States, the most common histology is adenocarcinoma, followed by squamous cell, large cell, and not otherwise specified. For patients with a preserved performance status (PS), double agent platinum-based therapy extends survival, improves quality of life (Qol), and reduces disease-related symptoms. The addition of a third cytotoxic agent increases toxicity without any clinical benefit. However, the addition of a targeted agent (bevacizumab, an antiangioegenesis agent, or cetuximab, an antibody against the epidermal growth factor receptor [EGFR]) to platinum-based therapy has yielded an improvement in survival compared with platinum-based therapy alone. To receive bevacizumab, patients are required to have nonsquamous histology, a PS of 0 or 1, and no evidence of brain metastases, hemoptysis, uncontrolled hypertension, and no need for therapeutic anticoagulation. The benefits of chemotherapy for patients with a poor performance status are less well defined, and the current recommendations are for treatment with single-agent chemotherapy. Elderly patients (defined as age > or = 70 yr) derive a survival and Qol benefit from chemotherapy treatment, and for the majority of elderly patients single-agent chemotherapy is the standard. However, elderly patients with a good performance status and without co-morbidities can tolerate platinum-based therapy without excessive toxicity and appear to derive a survival benefit similar to that in younger patients. Recently, a separate population of patients defined by a light or never-smoking history has been identified. This patient population appears to have unique clinical and molecular characteristics, and may benefit from initial therapy with an EGFR tyrosine kinase inhibitor. Once patients have progressed on first-line therapy there are three agents available (docetaxel, pemetrexed, and erlotinib), but the efficacy of pemetrexed appears to be limited to patients with nonsquamous histology. Despite the improvements in care and number of therapeutic agents available, the survival for patients with advanced-stage NSCLC remains modest; novel approaches are required and participation in clinical trials should be encouraged.
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PMID:Current treatments for advanced stage non-small cell lung cancer. 1934 93

Pulmonary toxicity is rarely seen with most commonly used targeted therapies. The endothelial growth factor receptor (EGFR) small-molecule tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib can cause interstitial lung disease (ILD). BCR-ABL tyrosine kinase inhibitors imatinib and dasatinib can cause pleural effusions. Infusion-related bronchospasm is common with the monoclonal antibodies to EGFR cetuximab and panitumumab, and case reports of bronchiolitis and pulmonary fibrosis have been described. Up to one-sixth of patients taking mammalian target of rapamycin (mTOR) inhibitors get a reversible interstitial pneumonitis. Bevacizumab, the monoclonal antibody to vascular endothelial growth factor (VEGF), has been associated with hemoptysis and pulmonary embolism particularly in patients with squamous cell lung cancer. Infusion-related bronchospasms, acute respiratory distress syndrome (ARDS), and interstitial pneumonitis can be seen with the anti-lymphocyte monoclonal antibodies rituximab, ofatumumab, and alemtuzumab. While most pulmonary toxicities from these therapies are mild and resolve promptly with dose reduction or discontinuation, it is important for the clinician to recognize these potential toxicities when faced with treatment-related complications. Discerning these pulmonary adverse effects may help in making decisions on diagnostic testing and therapy, particularly for those with pulmonary and cardiovascular co-morbidities.
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PMID:Pulmonary toxicities from targeted therapies: a review. 2207 88

Lung cancer is the leading cause of cancer-related death. Targeting the vascular endothelial growth factor (VEGF) pathways in combination with standard chemotherapy can improve response rate and survival in non-small cell lung cancer. Since October 2006, a new class of drugs targeting angiogenesis has been introduced for the treatment of advanced lung cancer. Bevacizumab, an antibody directly targeting VEGF was the first agent to be approved. Other small molecule tyrosine kinase inhibitors targeting the VEGF receptor are also active in the treatment of advanced lung cancer and are currently under development. Most of these new drugs are well tolerated though potentially significant toxicities such as haemoptysis and hypertension have been observed. This article will review these new-targeted anti-angiogenic agents with a focus on their use in lung cancer and on their important side effects.
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PMID:[Anti-angiogenic agents in the treatment of lung cancer: indications and toxicities]. 2240 11

Anti-angiogenic drugs and in particular anti-vascular endothelial growth factor (VEGF) agents have entered the clinical armamentarium against cancer. New unexpected toxicities have emerged. The incidence and the severity of these toxicities have a great variability in the different studies. Among them, bleeding is one of the most severe and difficult to manage. Bevacizumab retains the highest frequency of bleeding complications, in particular epistaxis, hemoptysis and gastrointestinal bleeding. Although a higher incidence of severe hemorrhages has not been consistently demonstrated during the treatment with bevacizumab, mild bleeding episodes appear clearly increased in the experimental arm of most trials. Cases of severe pulmonary hemorrhage were reported in patients with lung cancer; these events occurred mainly intra-tumor and were significantly associated with squamous cell histology. Trials with other small-molecule tyrosine kinase inhibitors like sunitinib or sorafenib showed an overall lower rate of bleeding complications, but still significantly higher than the control arm in many cases. The mechanisms of bleeding induced by anti-VEGF agents are complex and not yet fully clarified: the main hypothesis is that VEGF could promote endothelial cell survival and integrity in the adult vasculature and its inhibition may decrease the renewal capacity of damaged endothelial cells. Management of bleeding in patients treated with anti-VEGF agents is a challenging task because this complication is at least in part inherent to the efficacy of the drug and because there is also an increased risk of thrombosis, both arterial and venous. So far, only few preliminary data are available on a strategy to prevent hemorrhage and thrombotic event.
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PMID:Side effects of anti-angiogenic drugs. 2268 33

Pulmonary toxicity is a known complication of erlotinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors. It consists of diverse entities such as interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia and pulmonary fibrosis. In our report, an unusual case of an asymmetric interstitial lung disease was described. A 68-year-old female presented with resistant cough, hemoptysis and a right lung atelectasis on chest X-ray. She underwent selective bronchial artery embolization successfully after pharmaceutical therapy failed to stop hemoptysis. Flexible bronchoscope revealed that the opening of the right main bronchus was blocked completely by a neoplasm with a distance <2 cm to the carina and the sample of bronchoscopic biopsy confirmed the diagnosis of lung adenocarcinoma (cT3N2M0). Dyspnea and asymmetric interstitial lung disease in the nontumorous lung were noted on the 6th day of erlotinib therapy (150 mg daily) which had been efficacious in its anticancer effect. Discontinuing erlotinib use and treatment with corticosteroids could not relieve her symptoms. The patient deteriorated rapidly and died of progressive respiratory failure. We explored the mechanisms of asymmetric interstitial lung disease.
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PMID:Fatal asymmetric interstitial lung disease after erlotinib for lung cancer. 2288 62

Patients with SCLC (Small cell lung cancer) have been treated differently from those with NSCLC (New-small cell lung cancer) as a different disease. Recently, even patients with NSCLC are treated differently according to histological subtypes. This change is associated with the development of new drugs, particularly molecular-targeted drugs. Because Bevacizumab can cause serious adverse effects, patients with squamous cell carcinoma histology and a history of hemoptysis are contraindicated for this drug. Pemetrexed has been approved with an anti-mesothelioma drug and was confirmed to be effective for NSCLC. However, its efficacy was not equally proved among the histological subtypes; only adenocarcinoma patients showed shorter progression-free and prolonged survival periods. Regarding tyrosine kinase inhibitors, the targeted gene alterations occur specifically in adenocarcinoma. Based on these findings, the current therapeutic strategy for NSCLC is based on the histological subtype and mutational status of EGFR and ALK. In this article, transition of the therapeutic strategy for NSCLC, characteristics of targeted gene alterations and efficacies of the targeted therapy are reviewed.
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PMID:[Recent changes in the therapeutic strategy for NSCLC in association with new anti-cancer agents]. 2385 89


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