Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Advances in chemotherapeutic agents have led to improved outcomes for patients with metastatic colorectal cancer (CRC). Chemotherapies, however, are limited by their toxicities and lack of specificity. Aberrations in the regulation and expression of growth factors have been implicated in the development of CRC, and this understanding has led to the development of targeted agents. In 2004, two novel agents, bevacizumab and cetuximab, were approved by the US Food and Drug Administration for the treatment of metastatic CRC. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, and cetuximab, a human-mouse chimeric monoclonal antibody to the epidermal growth factor receptor, have changed the field dramatically. Bevacizumab appears to augment the efficacy of combination chemotherapy regimens for the treatment of metastatic CRC in both the first- and second-line settings, and the role of bevacizumab as part of adjuvant treatment is the subject of ongoing trials. However, because of the increased incidence of serious arterial thromboembolic events, gastrointestinal perforations, bleeding complications, and hypertension associated with bevacizumab, this agent is probably not indicated in all circumstances. Combination treatment with cetuximab and irinotecan appears appropriate in patients with advanced CRC who have failed irinotecan. Patients who are unable to receive additional irinotecan may be treated with cetuximab monotherapy. Positive epidermal growth factor receptor status by immunohistochemistry of a tumor specimen is presently mandated to determine candidacy for this therapy, although this assay appears to be suboptimal and newer assessment techniques to determine suitability for therapy must be developed. Phase III trials should shed light on the role of cetuximab in the first-line metastatic and adjuvant settings. Multitargeted strategies in CRC combining chemotherapy with bevacizumab and cetuximab are currently being explored. Further advances in the treatment of CRC are expected through continued scientific investigation and well-designed clinical trials.
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PMID:Targeted therapy in colorectal cancer. 1672 21

(1) The prognosis for metastatic colorectal cancer is grim. The best treatment results are obtained by adding irinotecan to first-line fluorouracil + folinic acid therapy and then oxaliplatin to second-line fluorouracil + folinic acid therapy (or the reverse sequence), but median survival time still fails to exceed 2 years. (2) Bevacizumab is a monoclonal antibody directed against vascular endothelial growth factor (VEGF), a mediator involved in angiogenesis. Bevacizumab is marketed in Europe for first-line treatment of metastatic colorectal cancer, in combination with fluorouracil + folinic acid (with or without irinotecan). (3) The clinical evaluation includes 3 comparative trials. A double-blind trial involving 813 patients compared the American IFL protocol (irinotecan + fluorouracil + folinic acid) + placebo with the IFL protocol + bevacizumab. Median survival time was shorter with IFL + placebo (15.6 versus 20.3 months), but the results are difficult to extrapolate to the situation in Europe, where the FOLFIRI protocol is used (irinotecan + fluorouracil + folinic acid). This protocol is more effective than the IFL protocol. (4) Another double-blind trial, involving 204 patients, compared another American protocol, fluorouracil + folinic acid + placebo, with fluorouracil + folinic acid + bevacizumab. Median survival time did not differ significantly between the groups (12.9 and 16.6 months). (5) A combined analysis of 3 comparative trials showed an increase in median survival time of 3.3 months (17.9 versus 14.6 months) when bevacizumab was added to a fluorouracil + folinic acid combination. An indirect comparison suggests that this is no better than adding irinotecan. (6) In second-line treatment, preliminary data from a trial of bevacizumab + FOLFOX 4 (oxaliplatin + fluorouracil + folinic acid) fail to show a tangible benefit for bevacizumab. (7) Bevacizumab adjunction to current chemotherapy protocols increased the frequency of some potentially serious reactions, such as cardiovascular disorders (hypertension, arterial thrombosis); tumour haemorrhage; intestinal perforation; wound healing; and haematological disorders (severe leukopenia, etc.). (8) In practice, there is no evidence that bevacizumab is any better than current European chemotherapy protocols for first-line treatment of metastatic colorectal cancer.
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PMID:Bevacizumab: new drug. Metastatic colorectal cancer: good in theory, not in practice. 1676 97

Bevacizumab, a recombinant, humanised monoclonal antibody against vascular endothelial growth factor, when used in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy as first-line treatment of metastatic colorectal cancer (CRC) improves survival. In a randomised, placebo-controlled Phase III study, the addition of bevacizumab to irinotecan/5-FU/leucovorin (IFL) resulted in significant improvement in survival compared with IFL alone, which led to its approval for first-line use in CRC. Bevacizumab also demonstrates improved efficacy in combination with 5-FU/LV over chemotherapy alone when data were pooled from two randomised Phase II studies utilising bevacizumab with 5-FU/leucovorin, and also in a third treatment arm of bevacizumab/5-FU/LV of a randomised Phase III study. More recently, in the second-line setting, bevacizumab in combination with FOLFOX improved survival from 10.8 to 12.9 months in the ECOG 3200 trial. Clinical activity with the addition of bevacizumab to oxaliplatin and either 5-FU or capecitabine-based regimens has also been shown in TREE-2, and activity with the combination of bevacizumab and the EGFR inhibitor cetuximab has been documented in BOND-2. In this study, bevacizumab was generally well-tolerated with no unexpected toxicities when combined with cetuximab. A few toxicities were uniformly encountered in all of the above studies, in particular grade 3 medically-manageable hypertension (3 - 16%). In addition, other toxicities were haemorrhage (2 - 9.3%), gastrointestinal perforation (1.5%), arterial thromboembolism (3.8%), wound healing (1 - 2%) and proteinuria (1 - 2%). As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities which can arise and to develop practice guidelines for their management. This review addresses the toxicities noted in trials using bevacizumab for the treatment of CRC and provides recommendations for toxicity management.
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PMID:Incidence and management of bevacizumab-related toxicities in colorectal cancer. 1677 93

In a dozen years of development, irinotecan (CPT11) became one of major therapeutics in the taking care of the metastatic colorectal cancer (CCRM). First used in monotherapy every three weeks, irinotecan has been later developed in association with 5FU and folinic acid according to two modalities of administration (bolus schedule administred weekly or infused schedule every two weeks). This association is now validated both in first and second line. Infused schedule (Folfiri) seems to introduce the best ratio of efficacy/tolerance. The association with the anti VEGF antibody (Avastin), bevacizumab) is promising. Moreover the association of the irinotecan with the anti EGFR antibody (Erbitux)), cetixumab) has show a efficacy in third line after progression under an protocol with irinotecan. Combinations with oxaliplatine (Irox, Irinox) or (Folfoxiri, Folfirinox) still remain in the course of appreciation notably in neoadjuvant context. An increment of dose seems accomplishable in monotherapy or in combination with/AF (high Folfiri doses) with a notable increment of responses rates. Nevertheless this strategy must again show a true clinical interest. Finally they are at promising developments in the fields of the irinotecan pharmacogenetic and pharmacogenomic.
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PMID:[Irinotecan for the treatment of metastatic colorectal cancer]. 1677 30

Among patients with colorectal cancer (CRC) diagnosed in the United States, 37.2% are diagnosed with stage III and 27.9% with stage II disease. In locoregionally advanced CRC, surgery is the primary treatment modality and has a curative intent. The survival depends on the pathologic stage and varies from 30%-60% for stage III to 60%-80% for stage II. However, as much as 40%-50% of patients will relapse and require additional treatment of the disease. Clinical failure after resection of CRC is predominantly secondary to the clinical progression of previously undetected distant metastatic disease. Until very recently, the absolute benefit for survival obtained with adjuvant therapy compared with control was about 6%. Introduction of oxaliplatin in the adjuvant setting has shown a reduction of 23% in the risk of relapse when compared with 5-fluorouracil alone (MOSAIC). Recent phase III studies have shown that targeted agents improved survival in patients with advanced-stage CRC. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is the first antiangiogenic drug to show improved efficacy when used in combination with irinotecan and oxaliplatin for first- and second-line treatment of CRC. Cetuximab, another monoclonal antibody targeting epidermal growth factor receptor, has shown efficacy in third-line therapy and promising results in first-line phase II studies. There is great interest in whether the biologic agents bevacizumab and cetuximab can improve survival in the adjuvant-therapy setting. This article reviews the adjuvant therapy for colon cancer and discusses the potential role and current trials involving the targeted agents.
Clin Colorectal Cancer 2006 May
PMID:Targeted agents for adjuvant therapy of colon cancer. 1679 91

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor that has demonstrated increased overall survival when added to standard chemotherapy regimens for metastatic colorectal cancer. Herein we report the cases of 2 patients who demonstrated prolonged survival times of almost 5 and 6 years, respectively, on various chemotherapy regimens that also included bevacizumab. Throughout most of their disease course, these patients maintained a good quality of life, with some adjustments of chemotherapy doses because of side effects. Bevacizumab was generally well tolerated in long-term use.
Clin Colorectal Cancer 2006 May
PMID:Long-term treatment with bevacizumab for patients with metastatic colorectal cancer: case report. 1679 94

Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosine-kinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.
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PMID:Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. 1684 97

Bevacizumab represents the first humanized monoclonal antibody with antiangiogenic properties which has been introduced in clinical oncology. The VEGF antagonist is used for the treatment of advanced colorectal cancer based on significant survivial benefits. Besides hypertension, proteinuria, wound healing disorders, bleeding and thromboembolic events appear to be related to bevacizumab. Optimization of combination therapy, new potential indications as well as pharmacoeconomic considerations represent the topics of current discussion regarding the novel monoclonal antibody.
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PMID:[Bevacizumab. Progress in cancer therapy by antiangiogenesis]. 1686 78

Angiogenesis and neovascularization are important mechanisms for tumor growth, progression and, subsequent metastasis. Cancer cells, as part of an inflammatory process, produce and induce multiple molecules (proangiogenic and antiangiogenic) from the surrounding stromal cells. Vascular Endothelial Growth Factor (VEGF) is the most relevant proangiogenic molecule among them. Many inhibitors of angiogenesis have been developed in the last years with the aim to block the tumor blood supply as a new anticancer strategy. Bevacizumab, an anti-VEGF, has been already approved for its use in colorectal cancer showing prolonged disease free survival as well as overall survival. It shows also important activity in breast, lung, ovarian and kidney cancer. Many others inhibitors are in advanced clinical development and show promising results as well. Current basic and clinical research in this field is generating great expectations for the future of cancer treatment.
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PMID:Inhibitors of angiogenesis. 1687 May 37


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