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), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin; Genentech Inc., South San Francisco, CA), a monoclonal antibody directed against VEGF, 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 produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone. Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that 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) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting.
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PMID:Non-small cell lung cancer and antiangiogenic therapy: what can be expected of bevacizumab? 1517 12

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

Bevacizumab is the first anti-angiogenic agent inhibiting vascular endothelial growth factor (VEGF) for treatment of patients suffering from cancer. Life-threatening hemoptysis is the most serious adverse effect of bevacizumab. The inhibition of VEGF is a possible mechanism involved in the destruction of normal lung tissue and subsequent hemoptysis. We report a case of bevacizumab-related hemoptysis and associated bronchoscopic findings that were successfully treated with rigid bronchoscopy and laser photocoagulation.
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PMID:Bronchoscopy for bevacizumab-related hemoptysis. 1736 26

Angiogenesis and its role in the growth and development of metastases has become a topic of increasing importance. In non-small cell lung cancer (NSCLC), vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, growth of the primary tumor, and development of metastases. In addition, elevated expression in tissue samples is a negative prognostic feature. For these reasons, VEGF is a worthy target for novel therapies. Recent clinical trials have shown that the anti-VEGF monoclonal antibody bevacizumab adds to the effect of chemotherapy in the metastatic setting. Hypertension and proteinuria are, as expected, commonly seen in this patient population, but the unexpected toxicity of life-threatening hemoptysis has also been observed. This makes careful patient selection especially important for this class of drugs. Our understanding of the VEGF pathway is increasing, as are the number of available targeted agents. In addition to the monoclonal antibody, bevacizumab, VEGF receptor tyrosine kinase inhibitors, multitargeted kinase inhibitors, and combination VEGF and epidermal growth factor receptor (EGFR) inhibition, are all being evaluated in NSCLC. Small phase I and II trials have suggested modest benefit when used alone; however, we now know that the anti-angiogenic therapies work best in combination with chemotherapy. The results of ongoing trials using these agents in combination with standard therapy will provide more insight into their potential benefit. As it is known that small tumors require angiogenesis to grow and metastasize, the use of anti-angiogenic therapies in the adjuvant setting may provide even greater benefit, and increase the potential cure rate in this population of patients. The results of well-designed phase III trials will be required to truly understand how to best use this class of targeted therapies in resectable and metastatic NSCLC.
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PMID:Inhibition of angiogenesis in the treatment of non-small cell lung cancer. 1789 8

Angiogenesis, formation of new vasculature, is critical to cancer growth. Agents that block angiogenesis, in particular bevacizumab, a monoclonal antibody that binds vascular endothelial growth factor, the key ligand in angiogenesis, have become an important option for many patients with non-small cell lung cancer (NSCLC). Activity was first demonstrated in Eastern Cooperative Oncology Group E4599, a large phase 3 trial that randomized patients with newly diagnosed, nonsquamous NSCLC to receive carboplatin/paclitaxel with or without bevacizumab at 15 mg/kg every 3 weeks. The study demonstrated significant improvements in response rate, progression-free survival, and overall survival with the addition of bevacizumab. Median overall survival improved from 10.3 to 12.3 months (p = 0.003). Significant toxic effects, including fatal hemoptysis, however, resulted in 15 treatment-related deaths in the bevacizumab arm. The beneficial results were recently confirmed in the European Avastin in Lung Cancer B017704 (AVAiL) trial. In AVAiL, patients with newly diagnosed nonsquamous NSCLC were randomized to receive cisplatin/gemcitabine with or without bevacizumab at doses of either 7.5 or 15 mg/kg every 3 weeks. Both doses resulted in statistically significant improvements in response rate and progression-free survival, but overall survival results have yet to be presented. Based on these encouraging results, the drug is now being studied in earlier-stage disease as neoadjuvant or adjuvant therapy and in locally advanced NSCLC. Exploration of the safety and efficacy of the drug in combination with other chemotherapeutics and targeted agents, and in previously excluded patient populations such as those with brain metastases, is also ongoing.
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PMID:Antibodies to vascular endothelial growth factor in non-small cell lung cancer. 1852 Feb 92

Bevacizumab is a humanized monoclonal antibody (mAb) to vascular endothelial growth factor (VEGF), a major proangiogenic factor in advanced solid tumors. Phase I and II trial results suggested that this agent was well tolerated and could be combined with standard regimens in various solid tumors. An initial randomized phase II trial in advanced non-small cell lung cancer (NSCLC) yielded positive results regarding the potential efficacy of this agent in combination with carboplatin and paclitaxel (CbP). It also identified a safety signal in patients with squamous histology, who appear to have a higher rate of serious and potentially life-threatening pulmonary hemorrhage. Because of this observation, patients with predominantly squamous histology were excluded from the pivotal phase III trials, as were patients with brain metastases and a history of significant hemoptysis. Two phase III trials comparing a standard platinum-based doublet with or without bevacizumab have been reported in advanced NSCLC, both of which met their primary endpoints. The trial reported by the Eastern Cooperative Oncology Group (ECOG 4599) was the first to show an overall survival benefit, as well as a benefit in response rates and progression-free survival resulting from the addition of bevacizumab to CbP. Certain toxicities were increased when bevacizumab was added to CbP, including neutropenia, febrile neutropenia, thrombocytopenia, bleeding (including pulmonary hemorrhage), hypertension and proteinuria. Bevacizumab is the first targeted therapeutic agent to improve survival in advanced NSCLC when added to standard chemotherapeutic regimens.
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PMID:Bevacizumab as first-line treatment for advanced non-small cell lung cancer. 1853 87

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

Bevacizumab is the first molecularly targeted agent associated with improved outcomes in combination with chemotherapy in previously untreated patients with non-small-cell lung cancer (NSCLC). The addition of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), to carboplatin and paclitaxel resulted in a significant improvement in overall survival compared with chemotherapy alone; however, bevacizumab is associated with increased risk of severe complications, including hemoptysis, neutropenic fever, and gastrointestinal perforation. Based on the initial observations that patients with squamous cell carcinoma treated with bevacizumab are at high risk for severe and fatal hemoptysis, these patients were not included in subsequent phase III clinical trials involving this agent. Patients with known brain metastases from lung cancer were excluded because of concern for intracranial bleeding. Consequently, nearly half the patients with newly diagnosed metastatic NSCLC are not treated with bevacizumab because of squamous histology or the presence of brain metastasis. This review provides a brief overview of the very limited data available regarding the safety and efficacy of bevacizumab and other VEGF inhibitors in patients with squamous cell histology or brain metastasis and current ongoing research efforts.
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PMID:Treatment of patients excluded from Eastern Cooperative Oncology Group 4599 and AVAiL studies: focus on brain metastasis and squamous histology. 2188

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


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