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

Approximately one half of prescribed radiotherapy is given for palliation of symptoms due to incurable cancer. Distressing symptoms including pain, bleeding, and obstruction can often be relieved with minimal toxic effects. Painful osseous metastasis is common in oncologic practice. Ninety percent of patients with symptomatic bone metastases obtain some pain relief with a lowdose, brief course of palliative radiotherapy. One half of the responding patients may experience complete pain relief. A single dose of 800 cGy in the setting of painful bone metastasis may provide pain control comparable to more protracted treatment at a higher dose of radiation. Patients with lytic disease in weight-bearing bones, particularly in the presence of cortical destruction, should be considered for prophylactic surgical stabilization of their condition. Routinely a brief, fractionated course of radiotherapy is given postoperatively. Pain due to multiple bone metastases uncontrolled by analgesics can be managed with single doses of halfbody irradiation. Doses of 600 cGy delivered to the upper half-body (above the umbilicus) and 800 cGy to the lower half-body (from the umbilicus to the middle of the femur) will provide some pain relief in 73% of patients. Half-body techniques have been investigated as prophylactic treatment, as a complement to local-field irradiation, and as fractionated rather than singledose therapy. Although intravenous administration of strontium 89 has been associated with myelosuppression, this treatment has been shown (a) to relieve pain due to bone metastasis and (b) to delay development of new painful sites. Recent data from phase III trials demonstrated that bisphosphonates have a role in reducing skeletal morbidity due to bone metastasis. Bone pain was reduced, and the incidence of pathologic fracture and the need for future radiotherapy was decreased. Radiotherapy relieves clinical symptoms in 70% to 90% of patients with brain metastases. Brief treatment schedules (e.g., 2000 cGy in five fractions over 1 week) are as effective as more prolonged therapy. Patients with solitary brain metastasis and no extracranial disease or controlled extracranial disease should be considered for surgical resection, because phase III data indicate enhanced survival with such an approach. Whole-brain radiotherapy is routinely administered postoperatively. A phase III study is examining the impact of accelerated fractionated doses of radiotherapy (two treatments per day) on survival of patients with brain metastases. Stereotaxic radiosurgical treatment is becoming increasingly available and permits delivery of radiation to metastatic intracranial tumor with minimal exposure of normal surrounding brain This treatment is most commonly used at the time of a solitary recurrence of disease in patients who previously received whole-brain radiotherapy. A role for this modality in newly diagnosed brain metastases remains to be defined. Chest symptoms are common in patients with locally advanced lung cancer and are effectively palliated with one 1000 cGy or two 850 cGy one fraction doses of radiation to the thoracic inlet and mediastinum. Chest pain and hemoptysis are more effectively palliated than cough and dyspnea. In patients with stage III cancer there is no compelling evidence that radiotherapy confers a survival advantage, and it may be reasonable to administer thoracic radiotherapy only when the patient has significant symptoms and the goal is to achieve control of these symptoms. Approximately 75% of the cases of superior vena cava syndrome are due to lung cancer, and small-cell lung cancer is the most common histologic type. A histologic diagnosis should be obtained before treatment is started, because detection of lymphoma or small-cell carcinoma would necessitate systemic therapy. Eighty percent of the patients with vena cava syndrome due to malignant disease achieve symptom relief with a brief, fractionated, palliative course of rad
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PMID:Radiotherapy for palliation of symptoms in incurable cancer. 920 88

Interferon (IFN)-alpha has been widely used in systemic therapy for advanced renal cell carcinoma (RCC). IFN-alpha is represented by a large family of structurally related genes expressing at least 14 subtypes, each of which shows quantitatively distinct patterns of biological activities. Although those distinct patterns of biological activities of IFN-alpha subtypes against renal cancer cell lines have been demonstrated, there is no report that demonstrates the difference in each subtype-induced antitumor activity in patients with RCC. Herein, we present a unique case of advanced RCC that is resistant to interleukin-2 and IFN-alpha administration, and we describe its response to another IFN-alpha administration. The difference between the two IFN-alpha types lies in the distribution of the subtypes: this case, therefore, suggests that the difference in the subtype distribution may cause the different response of the RCC. A 47 year-old male was diagnosed as left RCC with multiple lung metastases and underwent radical nephrectomy. The histological diagnosis was pT3b G2 clear cell carcinoma. He received intramuscular administration of 6 x 10(6) units of natural human IFN-alpha (Sumiferon) three times a week following the operation. However, the lung metastases showed progression. Thereafter, he received intravenous administration of 1.4 x 10(6) units of human interleukin-2 everyday. However, the lung metastases showed further progression and the hemoptysis, dyspnea, and chest pain deteriorated. Finally, he was given intramuscular administration of 5 x 10(6) units of another natural human IFN-alpha (OIF) three times a week. After the OIF administration, his complaints subsided and a chest CT scan revealed reduced lung metastases and diminished pleural effusion. He had not received any anti-tumor agents other than IFN-alpha or interleukin-2 since the operation. However, although he remained free of hemoptysis, dyspnea, and chest pain after OIF administration, the lung metastases increased again and multiple brain metastases were also observed five months after the first OIF administration. He died of metastatic RCC one year after the operation.
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PMID:[Advanced renal cell carcinoma showing a different response to two types of interferon-alpha]. 1497 41

Angiogenesis, the growth of new vessels from preexisting vessels, is a fundamental step in tumor growth and progression. Vascular endothelial growth factor (VEGF) is a key angiogenic factor implicated in tumor blood vessel formation and permeability. Overexpression of VEGF has been observed in a variety of cancers and has been associated with a worse relapse-free and overall survival. The antiangiogenic agent bevacizumab, a monoclonal antibody directed against VEGF, has shown clinical benefit in multiple cancers, including non-small cell lung cancer (NSCLC). Based on the favorable results of a prior randomized, phase II trial, the Eastern Cooperative Oncology Group conducted a trial (E4599) to evaluate the efficacy of bevacizumab in combination with paclitaxel and carboplatin in patients with recurrent or advanced stage IIIB or IV nonsquamous cell NSCLC. Exclusion criteria included squamous cell histology, brain metastases, significant hemoptysis, or inadequate organ function or performance status >1. The primary study end point was overall survival. The median duration of survival in the chemotherapy plus bevacizumab group was 12.3 months compared with 10.3 months in the chemotherapy alone group (P = 0.003). Significant bleeding was more frequent in the chemotherapy plus bevacizumab group, 4.4% compared with 0.9% (P = 0.001). There were 15 treatment-related deaths in the chemotherapy plus bevacizumab group, including 5 due to pulmonary hemorrhage. Future and current directions include evaluation of bevacizumab in earlier stages of NSCLC, in SCLC, and in combination with other targeted agents, such as erlotinib.
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PMID:Bevacizumab in non small cell lung cancer. 1767 Nov 51

The development of brain metastases originating from colorectal cancer (CRC) is an infrequent phenomenon occurring in < 5% of patients. Yet, it is feasible that physicians will be diagnosing more patients with brain metastases because of the prolonged survival in our current patient population. The anti-angiogenic agent bevacizumab is currently approved in bevacizumab-naive patients with metastatic CRC (mCRC). Initially, precautionary measures regarding the use of bevacizumab were recommended for patients at risk of bleeding based on earlier incidents of intracranial hemorrhage, hemoptysis, and pulmonary hemorrhage. However, recent data support the use of bevacizumab in the treatment of high-grade gliomas. We present a challenging case of a treatment-naive patient with mCRC with brain metastases and the challenges involved in weighing the risks and benefits of systemic chemotherapy when combined with a biologic agent.
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PMID:Bevacizumab in the treatment of a patient with metastatic colorectal carcinoma with brain metastases. 1827 80

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

Choriocarcinoma is an aggressive tumour. Uncommonly, it spreads distantly, and rarely results in pulmonary and brain metastases. Its prognosis is generally good when treated. We report a 33-year-old woman with fever, haemoptysis and asthenia. One month after the appearance of metrorrhagia, she was diagnosed to have choriocarcinoma with pulmonary metastasis. After chemotherapy, pulmonary images disappeared and human chorionic gonadotropin returned to normal. She was re-admitted with neurological signs ten months later, confirming recurrence of the disease with brain metastasis. She was treated with surgery and polychemotherapy, with a favourable outcome and disappearance of the disease.
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PMID:Choriocarcinoma with pulmonary and cerebral metastases. 1894 1

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

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

The recent approval of bevacizumab, sunitinib, and sorafenib in a number of diseases has led to significant interest in expanding the role of antiangiogenic therapies in cancer. Specifically, bevacizumab has only received approval for a relatively selective population with advanced non-squamous non-small-cell lung cancer (NSCLC) with good performance status and without coagulopathy, brain metastases, or hemoptysis. This has significantly restricted the potential benefit bevacizumab can bring to patients with lung cancer. In order to address whether bevacizumab might be beneficial in other settings, a multitude of clinical trials are ongoing. These include questions such as the safety of bevacizumab in patients with hemoptysis, brain metastases, and squamous cell histology. The use of bevacizumab is also being addressed in locally advanced and early-stage lung cancer. The results of many of these trials will be available in the next 2-3 years. Unfortunately, as in the case of many targeted therapies, we lack a specific biomarker to predict response to these agents. In addition, although antiangiogenic trials are well under way in NSCLC, this is not the case for small-cell lung cancer, a highly angiogenic disease in which the pace of research is substantially slower.
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PMID:Ongoing trials with bevacizumab and other antiangiogenic agents in lung cancer. 2188 2


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