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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past decade, metastatic colorectal cancer has evolved from a relatively resistant disease to one that is sensitive to a variety of chemotherapeutic drugs and combinations of drugs. During the same period, the median survival of patients with metastatic colorectal cancer increased from approximately 14 months to almost 20 months. First-line chemotherapy prolongs survival and delays the appearance of symptoms and should be considered in patients who are still asymptomatic. Patients with metastatic colorectal cancer and adequate performance status should be treated with a combination of fluorouracil (5-FU) and either oxaliplatin or irinotecan. Bevacizumab, the monoclonal antibody against the vascular endothelial growth factor, has been shown to prolong survival with acceptable toxicity and may be added when available. When the disease recurs, second-line chemotherapy may also prolong survival in appropriately selected patients. Typically, treatment includes 5-FU and one of the drugs not used in the first-line therapy (oxaliplatin or irinotecan). Several oral prodrugs of 5-FU are currently available. Capecitabine, approved in the United States, may be safely substituted for 5-FU in the majority of settings and combinations. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor and is approved both as a single agent and in combination with irinotecan for patients with recurrent disease. This treatment may represent a second-line or third-line option in selected patients. Treatment of patients with isolated liver metastases may also include surgical or other ablative procedures. In carefully selected patients, these modalities add to the efficacy of chemotherapy and may be used with potentially curative intent. However, for the vast majority of patients with metastatic colorectal cancer treatment is palliative.
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PMID:Chemotherapy of Metastatic Colorectal Cancer. 1591 13

The improved survival associated with adding the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to chemotherapy for the treatment of patients with metastatic colorectal cancer demonstrates the importance of targeting collateral cells involved in tumor growth, progression, and metastatic spread. Based on the Gompertzian model of tumor growth, adding anti-VEGF agents to standard chemotherapy may be especially effective in early stages of cancer. By improving chemotherapy delivery to the tumor and inhibiting regrowth between treatment cycles, anti-VEGF agents may alter the growth pattern of a tumor such that it is more susceptible to eradication. These concepts also suggest that anti-VEGF agents could enhance the effectiveness of chemotherapy given conventionally or in a dose-dense fashion. As such, it is possible that the effectiveness of chemotherapy could be maintained or improved, even at lower cumulative doses, which may improve its tolerability. Additionally, the effects of anti-VEGF agents on metronomic chemotherapy, which is reported to have antiangiogenic properties on its own, warrant further evaluation. Preclinical data demonstrate that cytostatic angiogenesis inhibitors are potent complementary agents to metronomic chemotherapy, producing sustained complete regressions in some models of human cancer. Dose-dense and metronomic chemotherapy have in common a shortened dosing interval and resultant increased and/or prolonged exposure of tumor cells to chemotherapy in vivo. Optimizing the use of anti-VEGF agents in the clinic demands further investigation of the most appropriate way to combine them with chemotherapy, particularly regimens designed to exploit known tumor growth patterns and those designed to target the endothelial cells involved in neovascularization with multiple agents.
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PMID:Clinical implications of antiangiogenic therapies. 1593

Angiogenesis is crucial to tumour initiation, survival and metastasis. Vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors in cancer development. Bevacizumab (a humanised monoclonal antibody against VEGF) has a reasonable safety profile and proven efficacy in a phase III trial in advanced colorectal cancer. Efficacy of Bevacizumab also looks promising in non small cell lung cancer, renal cancer and a variety of other solid tumours. Questions still surround optimal dosing and the appropriate selection of patients who are most likely to benefit. Future trials will address these questions and provide further translational insights.
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PMID:Bevacizumab--current status and future directions. 1677 23

Significant advances have been made in the treatment of advanced colorectal cancer over the past 5 years, namely due to the introduction of three novel cytotoxic agents-capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin (Eloxatin)-and the recent approval of two biologic agents-bevacizumab (Avastin) and cetuximab (Erbitux). During this time period, the median survival of patients with advanced, metastatic disease has gone from 10 to 12 months to nearly 24 months. Intense efforts have focused on identifying novel targeted therapies that target specific growth factor receptors, critical signal transduction pathways, and/or key pathways that mediate the process of angiogenesis. Recent clinical trial results suggest that the anti-VEGF antibody bevacizumab can be safely and effectively used in combination with each of the active anticancer agents used in colorectal cancer. Despite the development of active combination regimens, significant improvements in the actual cure rate have not yet been achieved. Combination regimens with activity in advanced disease are being evaluated in the adjuvant and neoadjuvant settings. The goal is to integrate these targeted strategies into standard chemotherapy regimens so as to advance the therapeutic options for the treatment of advanced colorectal cancer. Finally, intense efforts are attempting to identify the critical molecular biomarkers that can be used to predict for either clinical response to chemotherapy and/or targeted therapies and/or the drug-specific side effects. The goal of such studies is to facilitate the evolution of empiric chemotherapy to individually tailored treatments for patients with colorectal cancer.
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PMID:Current therapies for advanced colorectal cancer. 1594 40

Many elderly individuals have substantial life expectancy, even in the setting of significant illness. There is evidence to indicate that elderly individuals derive as much survival benefit as younger patients from standard chemotherapy approaches in advanced colorectal cancer. Effective treatments should not be withheld from older patients on the basis of age alone. Treatment decisions should be based on functional status, presence of comorbidities, and consideration of drug-specific toxicities that can be exacerbated in older individuals due to decreased functional reserve. Infusional and weekly fluorouracil (5-FU) regimens are better tolerated than bolus and monthly regimens. Oral capecitabine (Xeloda) reduces the frequency of a number of toxicities compared with bolus 5-FU, including stomatitis, a particularly debilitating toxicity in many elderly patients. The effectiveness and tolerability of oxaliplatin and irinotecan (Camptosar) appear to be similar in older and younger patients. Older patients can also receive bevacizumab (Avastin), although caution is warranted in those with cardiovascular disease. Overall survival in metastatic colorectal cancer improves with the availability of multiple effective chemotherapeutic agents. The full range of effective therapies in advanced colorectal cancer should be extended to elderly patients.
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PMID:Management of advanced colorectal cancer in older patients. 1594 41

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in vivo. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high affinity VEGF receptors. VEGF plays an essential role in developmental angiogenesis and is important also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with VEGF inhibitors in a variety of malignancies are ongoing. Recently, a humanized anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the FDA as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.
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PMID:Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. 1595 88

Bevacizumab (Avastin; Genentech/Roche), an antibody against vascular endothelial growth factor, was approved by the US FDA in February 2004 for the first-line treatment of metastatic colorectal cancer in combination with 5-fluorouracil-based chemotherapy. It is the first approved agent to target tumour angiogenesis.
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PMID:Bevacizumab. 1596 23

Bevacizumab is a humanised monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), the key mediator of tumour angiogenesis, and has been shown to improve survival when given with chemotherapy to patients with metastatic colorectal cancer. In a pivotal Phase III clinical trial, 813 subjects were treated with irinotecan, 5-fluorouracil (5-FU) and leucovorin and randomised to receive placebo or bevacizumab. Median survival for the group receiving bevacizumab was increased by 30%, from 15.6 to 20.3 months (p < or = 001). Other Phase II and III studies in colorectal cancer have demonstrated a benefit when bevacizumab is added to regimens of 5-FU and leucovorin, and 5-FU, leucovorin and oxaliplatin. The toxicity associated with bevacizumab is generally mild, consisting of manageable hypertension, clinically insignificant proteinuria and mild mucosal bleeding. Infrequent severe toxicities have been reported, consisting of arterial thrombosis and gastrointestinal perforations (1.5%). Bevacizumab represents the first angiogenesis modulator that has a proven benefit in cancer therapy.
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PMID:Bevacizumab in the treatment of colorectal cancer. 1601 43

From having been a 'single-drug not very interesting cancer type' from a medical treatment perspective, treatment of colorectal cancer (CRC) has during the past five years become a more complex issue of the appropriate use of several cytotoxic drugs sometimes integrated with advanced metastatic surgery with curative intent. The new drugs have provided significant benefit to the patients, so far mostly in the metastatic setting but also in adjuvant treatment. The significant progress in molecular and tumour biology has produced a great number of new 'targeted' drugs that are now in various stages of clinical development. Two of these drugs, the monoclonal antibodies bevacizumab (Avastin) and cetuximab (Erbitux), directed against VEGF and EGFR, respectively, have recently been approved within the EU for use in metastatic CRC. This Nordic Expert Consensus Report summarizes the current status of chemotherapy in metastatic CRC, overviews the clinical status of targeted drugs in CRC and, finally, provides guidelines for the routine clinical use of bevacizumab and cetuximab based on the most recently available clinical data.
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PMID:Targeted drugs in metastatic colorectal cancer with special emphasis on guidelines for the use of bevacizumab and cetuximab: an Acta Oncologica expert report. 1607 90

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


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