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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor promotes angiogenesis, an important mediator of growth and metastasis in human breast cancer. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, is under investigation as an anti-angiogenic agent. This phase I/II trial evaluated the safety and efficacy of bevacizumab in patients with previously treated metastatic breast cancer. Seventy-five patients were treated with escalating doses of bevacizumab ranging from 3 mg/kg to 20 mg/kg administered intravenously every other week. Tumor response was assessed before the sixth (70 days) and 12th (154 days) doses. Safety was evaluated during every cycle. Eighteen patients were treated at 3 mg/kg, 41 at 10 mg/kg, and 16 at 20 mg/kg. Four patients discontinued study treatment because of an adverse event. Hypertension was reported as an adverse event in 17 patients (22%). The overall response rate was 9.3% (confirmed response rate, 6.7%). The median duration of confirmed response was 5.5 months (range, 2.3 to 13.7 months). At the final tumor assessment on day 154, 12 of 75 patients (16%) had stable disease or an ongoing response. The optimal dose of bevacizumab in this trial was 10 mg/kg every other week and toxicity was acceptable. These data support the initiation of trials in metastatic breast cancer combining bevacizumab with chemotherapy.
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PMID:A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. 1461 32

Targeted therapy for breast cancer has existed since 1986, when Beatson published his observations on oophorectomy. In the past 5 years monoclonal antibodies and tyrosine kinase inhibitors have been evaluated in phase I and II clinical trials of breast cancer. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) was the first such agent to be approved by the US Food And Drug Administration, following findings that it improved survival in patients with metastatic breast cancer. Gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE) has little activity as a single agent in unselected patients, but, preclinical data have suggested synergy with tamoxifen and other hormonal agents, as well as other growth factor inhibitors. Bevacizumab (Avastin; Genentech, Inc), a monoclonal antibody against vascular endothelial growth factor is being evaluated in metastatic breast cancer. Furthermore, agents targeting other pathways, such as the Ras pathway with farnesyl transferase inhibitors, and mTOR with rapamycin analogues are currently under investigation. In the next few years, and as trials with the above agents mature, we will further define the role of these targeted agents in the treatment of breast cancer.
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PMID:New targeted therapies in breast cancer. 1512 30

Vascular endothelial growth factor (VEGF) has emerged as a key target for the treatment of cancer. As the ligand to the VEGF receptor, it plays a central role in promoting tumor angiogenesis. Overexpression of VEGF leads to poor outcomes in patients with breast cancer and other tumors. Preclinical studies have shown that the humanized monoclonal antibody to VEGF, bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), can reduce tumor angiogenesis and inhibit the growth of solid tumors, either alone or in combination with chemotherapy. As a single agent or added to vinorelbine, bevacizumab has produced encouraging results in phase II clinical trials in patients with refractory metastatic breast cancer. When added to capecitabine chemotherapy in a phase III trial, bevacizumab produced a greater response rate, but did not prolong progression-free survival. This may reflect the late disease stage and poor prognostic factors in the patient population. A large, ongoing, phase III, cooperative group trial is evaluating the effect of bevacizumab in combination with paclitaxel as first-line therapy for metastatic disease. The adverse effect profile of bevacizumab differs from that of cytotoxic chemotherapy and includes hypertension, proteinuria, thrombosis, and epistaxis.
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PMID:Bevacizumab in the treatment of breast cancer: rationale and current data. 1517 15

Within the revolution of molecular biology in cancer, it should be pointed out the role of monoclonal antibodies clinically utilized as if they were "magic bullets". From the works of Kohler and Milstein in 1975 the evolution has been fast and its inclusion in daily clinical practice gradual. Among the more significant there is anti-CD20 that has revolutionized the treatment of lymphomas. Currently, antibodies conjugated with isotopes derived from anti-CD20 have been produced. Trastuzumab antibody against HER2/neu has opened new prospects in the treatment of breast cancer. Cetuximab antibody against EGFR has achieved good results in the treatment of chemotherapy-resistent colon cancer. Bevacizumab is perhaps the most promising antibody against solid tumors, having shown effectiveness as first line therapy in metastatic colon cancer in combination with chemotherapy.
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PMID:[Antibodies against cancer]. 1571 74

The field of cancer research has seen a marked shift in the past decade towards the exploration and development of non-conventional antitumour agents. One of the most widely studied approaches to therapy during this period has been that of antiangiogenesis. The published clinical trials and subsequent FDA approval (in February 2004) of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin, Genentech) for the treatment of colorectal cancer marked a milestone for antiangiogenesis therapy. Currently, preclinical and clinical research involving therapeutic targeting of VEGF and other mediators of angiogenesis continues in multiple tumour types. In addition to colorectal cancer, angiogenesis inhibitors are being investigated in the treatment of renal cell carcinoma, head and neck carcinoma, lung cancer, breast cancer, prostate cancer, and a variety of haematological malignancies. This article will discuss the background of antiangiogenesis research, preclinical and clinical data relating to the use of bevacizumab in the treatment of colorectal cancer, other completed clinical trials involving antiangiogenesis agents, and the potential future utility of these agents in the treatment of malignancy.
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PMID:Angiogenesis inhibitors in the treatment of cancer. 1608 56

The treatment of cancer by targeting angiogenesis and depriving growing tumors of their blood supply has been recognized as an interesting therapeutic possibility for several decades. A multitude of development programs investigating both low-molecular-weight substances and biologicals, in particular monoclonal antibodies (mAbs), have been instigated. The generation of human or human-like mAbs has led to the recent development of therapeutic antibodies that are potentially highly beneficial in the treatment of cancer. Avastin, which binds to the pro-angiogenic factor vascular endothelial growth factor, is one of the most promising of these antibodies, and has proved beneficial in the treatment of colorectal, lung and breast cancer, with a potential to be used also in other types of cancer. However, as angiogenesis is a complex process controlled by both pro-angiogenic as well as anti-angiogenic factors, several research and development programs targeting different pro-angiogenic factors, receptors and antigens that are selectively expressed on cells in newly formed blood vessels are under way. At BioInvent International AB, research is focused on angiomotin, a newly discovered receptor for the anti-angiogenic factor angiostatin, and on the pro-angiogenic factor placenta growth factor.
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PMID:Targeting angiogenesis with antibodies for the treatment of cancer. 1611 94

The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting.
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PMID:Monoclonal antibody therapy of cancer. 1615 8

Bevacizumab (Avastin) is a humanized recombinant antibody that prevents vascular endothelial growth factor (VEGF) receptor binding, and inhibits angiogenesis and tumor growth. In patients receiving an irinotecan plus fluorouracil/leucovorin (IFL) regimen for first-line treatment of metastatic colorectal cancer, the addition of bevacizumab significantly increased overall survival by 4.7 months relative to IFL plus placebo. In the second-line treatment of advanced colorectal cancer, patients who received bevacizumab in combination with a fluorouracil/leucovorin plus oxaliplatin (FOLFOX4) regimen had an overall survival time that was 2 months longer than that in patients receiving FOLFOX4. Preliminary results indicated that bevacizumab significantly extended progression-free survival by 4.9 months in patients receiving paclitaxel for the first-line treatment of locally recurrent or metastatic breast cancer. The addition of bevacizumab to paclitaxel plus carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) significantly prolonged overall survival by >2 months. Bevacizumab has acceptable tolerability in patients with advanced colorectal cancer, breast cancer, or NSCLC, with the majority of adverse events being generally mild and clinically manageable. Thus, bevacizumab provides a highly effective addition to standard chemotherapeutic regimens for advanced colorectal cancer, breast cancer, and NSCLC.
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PMID:Spotlight on bevacizumab in advanced colorectal cancer, breast cancer, and non-small cell lung cancer. 1672 68

Preoperative chemotherapy for operable breast cancer has been evaluated in a number of series. The recombinant humanized anti-human VEGF monoclonal antibody (rhuMAb, bevacizumab) inhibits several activities of VEGF, including endothelial cell growth, vascular permeability and angiogenesis. Synergy with many cancer chemotherapeutic agents, was observed in preclinical studies and in phase I and phase II trials and confirmed in phase III trials. Bevacizumab has also been tested in breast cancer in the neoadjuvant setting with encouraging results. Based on the synergism of bevacizumab in combination with chemotherapy, we will investigate the efficacy of bevacizumab in modulating the proliferation rate of locally advanced operable breast tumors treated with primary therapy.
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PMID:Primary systemic therapy on local advance breast cancer, where are we going? 1676 Feb 85

The recent development of monoclonal antibodies targeting growth factor receptors in cancer treatment represents a milestone for both researchers and physicians. Advances in the understanding of key molecular pathways for tumour growth and survival have facilitated the development of these targeted therapies, in particular in breast cancer. This review focuses on the three most important recombinant humanised monoclonal antibodies that have shown activity in women with breast cancer: trastuzumab, pertuzumab and bevacizumab. Trastuzumab, an anti-erbB2 (human epidermal growth factor receptor) monoclonal antibody, is currently routinely used in both the metastatic and adjuvant settings for patients with erbB2-positive tumours. Pertuzumab, a monoclonal antibody binding to a different epitope on erbB2 than trastuzumab, is under early clinical evaluation. This drug has been developed for breast cancer patients, whether overexpressing erbB2 or not. Bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor-A, is being evaluated in the metastatic setting for its antiangiogenic properties, and is showing promising results.
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PMID:Monoclonal antibody-based targeted therapy in breast cancer: current status and future directions. 1695 5


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