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

For the past several decades, the therapy for metastatic colorectal cancer had modest benefits because of the limited therapeutic options. Bolus 5-fluorouracil (5FU) and leucovorin (LV) were the standard of care in the United States until 2002, with a response rate of 25% and a median survival of 10 to 12 months. However, with the advent of new agents, namely oxaliplatin and irinotecan, there has been a dramatic change in the way we treat metastatic colorectal cancer. Based on many well-conducted large randomized trials, we have evidence that combination chemotherapy incorporating oxaliplatin or irinotecan with infusional 5FU/LV is superior to 5FU/LV, with doubling of overall survival (OS) to approximately 20 months. There remains some uncertainty as to the best first-line regimen. This might be irrelevant because studies have shown that OS is dependent on exposure to all the active agents, regardless of the time period of exposure. Bevacizumab, which uses anti-angiogenic strategies, has improved disease-free survival (DFS) and OS when combined with standard chemotherapy and is a vital component of metastatic colorectal cancer therapy. However, there are no data supporting its use past progression. Cetuximab, an epithelial growth factor receptor inhibitor, is mainly used in irinotecan-refractory patients. In spite of all these advances, 5-year OS rates continue to be limited. Patients with curative resection of metastatic disease seem to have longer DFS and better 5-year OS rates. This should be a potential goal for responding patients with upfront unresectable, organ-limited disease.
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PMID:Metastatic colorectal cancer: Therapeutic options. 1690 56

Avastin (Bevacizumab) is a recently developed monoclonal antibody against vascular endothelial growth factor (VEGF) receptor that increases survival in patients with metastatic colorectal cancer. Bowel perforation is a known risk factor of unknown etiology associated with the use of Avastin. In this report, the incidence, risk factors, typical presentation, and management of patients with this complication is described.
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PMID:Bowel perforation from bevacizumab for the treatment of metastatic colon cancer: incidence, etiology, and management. 1697 Dec 5

A growing understanding of the molecular mechanisms involved in cancer biology and continuous refinement of available technologies for drug discovery have prompted the development of new therapeutic tools targeting specific cancer-associated molecular pathways. Among these so-called biological therapies, monoclonal antibodies have now reached the time of clinical application. Besides initial development of the murine antibody edrecolomab, the impact of monoclonal antibodies on cancer therapy has recently been clearly demonstrated in colorectal cancer by targeting two major pathways critical to tumourigenesis: the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signalling pathways. These antibodies showed significant clinical activity in advanced colorectal cancer, especially when combined with chemotherapy. This paper reviews the status of the monoclonal chimeric antibody cetuximab (Erbitux) and other anti-EGFR antibodies, and of bevacizumab (Avastin; an anti-VEGF humanised monoclonal antibody), in colorectal cancer treatment.
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PMID:Recent developments in colorectal cancer treatment by monoclonal antibodies. 1704 15

Bevacizumab (Avastin) in combination with intravenous 5-fluorouracil-based chemotherapy as first-line as well as second-line treatment of metastatic colorectal cancer improves survival. Although skin rash (type unspecified) has been described in some patients following infusion of bevacizumab, it is not a common toxicity of bevacizumab, while acneiform rash occurs in more than 90% of patients who receive cetuximab (Erbitux), the severity of which appears to be predictive of response. We report a patient with colorectal cancer who developed a rash secondary to bevacizumab that correlated with response. A 40-year-old patient with stage IV colorectal cancer received FOLFOX-4 and bevacizumab, which he tolerated very well except for a skin rash related to bevacizumab. The rash cleared every time bevacizumab was eliminated from the chemotherapy regimen. When use of bevacizumab was resumed, similar rash reappeared. Therefore, we believe that this observation of the rash emergence was linked to bevacizumab administration. The most common toxicities associated with bevacizumab include hypertension, hemorrhage, gastrointestinal perforation, arterial thromboembolism, wound healing and proteinuria. Exfoliative dermatitis and a nonspecific rash have been reported with bevacizumab. This case report, we believe, is the first report of a possible correlation between a rash and a positive drug response associated with bevacizumab, and may initiate further investigation of similar observation.
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PMID:Skin rash secondary to bevacizumab in a patient with advanced colorectal cancer and relation to response. 1707 24

Monoclonal antibodies are a new class of agents targeting at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can cany substances, such as radioactive isotopes, toxins and antineoplastic agents, to the targeted cells. Two of them, cetuximab (Erbitux) and bevacizumab (Avastin), seem to have acquired a significant role in the management of patients with radically resected and advanced colorectal carcinoma. Cetuximab plus irinotecan has been approved as second-line therapy in irinotecan-resistant colorectal cancer patients; bevacizumab plus 5FU/LV has resulted in higher response and longer survival than 5FU/LV alone in first line metastatic colorectal cancer; its combination with oxaliplatin has recently doubled results. The superior therapeutic efficacy of these molecular targeting agents over traditional chemotherapy has been shown by the survival benefit achieved by patients with advanced or recurrent cancers. Although the precise molecular mechanism by which these agents produce or enhance an antitumour effect, alone or in combination with anticancer drugs, is unknown, the specific inhibition of target genes critically involved in tumour progression and metastasis is clear. Further studies to determine which patient groups and anticancer drugs are more appropriate for combination therapy with these agents are needed. All the most important data obtained through recent studies are discussed, emphasizing their mechanisms of action, safety profiles and clinical applications.
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PMID:Recent progress in target therapy in colorectal cancer. 1709 29

Recent years have brought significant advances in the treatment of metastatic colorectal cancer. Combination regimens with standard chemotherapeutic agents have extended survival to nearly 2 years, and recent studies suggest that chemotherapy-free intervals may be feasible in some patients without compromising survival outcomes. The most significant recent progress has centered on the use of targeted biologic therapies. The first targeted agent to show a significant benefit in metastatic colorectal cancer was bevacizumab. This monoclonal antibody is directed against vascular endothelial growth factor, a molecule known to be involved in the angiogenic process that is central to cancer growth and metastasis. In clinical trials, bevacizumab has improved survival when added to multiple chemotherapy regimens. The second targeted agent to be approved for colorectal cancer is the monoclonal antibody cetuximab, which is directed against the epidermal growth factor receptor, another key mediator of cancer growth. Cetuximab has been shown to increases the efficacy of irinotecan in irinotecan-refractory patients, indicating that cetuximab may make tumors more sensitive to chemotherapeutic agents. Bevacizumab and cetuximab continue to be evaluated alone as maintenance therapy and in combination in different settings to determine their optimal use in colorectal cancer. Additional targeted agents are also being developed and are showing promise in clinical trials.
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PMID:The role of targeted therapy in the treatment of colorectal cancer. 1713 41

There are several treatment options for patients with metastatic colorectal cancer (mCRC), including those with disease that has progressed after treatment with chemotherapy. Bevacizumab-containing regimens show good efficacy in patients with previously treated disease. Compared with infused 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4), overall survival and progression-free survival are significantly longer with FOLFOX-4 in combination with bevacizumab as second-line treatment in patients with advanced or mCRC. In addition, the response rates and time to progression are greater with the combination of bevacizumab, cetuximab, and irinotecan in patients with irinotecan-refractory mCRC compared with cetuximab and irinotecan therapy. This combination is well tolerated, with no additive toxicities reported. The role of bevacizumab in the treatment of patients with disease refractory to 5-fluorouracil, irinotecan, and oxaliplatin is less clear, owing to inconclusive results in a multicenter study in this population. More research is necessary to determine the efficacy of combinations with bevacizumab in the third- and later-line settings. However, bevacizumab clearly provides significant clinical benefits in previously treated patients with mCRC. On the basis of these benefits and in addition to its approval in the first-line setting, bevacizumab in combination with intravenous 5-fluorouracil-based chemotherapy recently received US Food and Drug Administration approval for the second-line treatment of patients with mCRC.
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PMID:Bevacizumab in the treatment of metastatic colorectal cancer (mCRC) in second- and third-line settings. 1714 20

Bevacizumab is well suited for use in combination with first- or second-line chemotherapy in the treatment of metastatic colorectal cancer because its side effects are predictable and appear not to add to the incidence or severity of the side effects of chemotherapy. Clinical trials of bevacizumab in combination with oxaliplatin-containing and 5-fluorouracil-based regimens have shown that combination therapy is well tolerated and its toxicity is not substantially greater than that of the chemotherapy alone. Preliminary data from community-based and observational studies show that the incidence and severity of adverse events with combinations of bevacizumab and newer chemotherapy regimens are similar to those in the pivotal phase III trial with irinotecan, 5-fluorouracil, and leucovorin plus bevacizumab. Across trials, these side effects include a greater risk of grade 3 hypertension and grade 1 or 2 proteinuria, a slight increase (<2 percentage points) in grade 3 or 4 bleeding, and impaired surgical wound healing in patients who undergo surgery during treatment with bevacizumab. Potentially life-threatening events (arterial thrombotic events and gastrointestinal perforation) have occurred in a small number of patients. Close patient monitoring, especially in patients who are at greater risk of adverse events, is important.
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PMID:Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse events. 1714 22

Bevacizumab, the first approved vascular endothelial growth factor (VEGF)-targeted agent for metastatic colorectal cancer, continues to be developed in phase III trials in other tumor types. Its use is being explored not only in advanced disease, but also in earlier-stage disease in the adjuvant setting. Preclinical and clinical research is also addressing several potential strategies for maximizing the benefits of bevacizumab and other VEGF-targeted agents, including (1) dual inhibition of VEGF and platelet-derived growth factor signaling to target both the endothelial and the pericyte components of tumor vasculature; (2) combining VEGF-targeted agents with other targeted agents, such as inhibitors of HER2 or epidermal growth factor receptor signaling, which affect several angiogenic pathways; and (3) combining VEGF-targeted agents with low-dose, metronomic chemotherapy. The optimal dose and schedule of VEGF-targeted agents is another unanswered question. Further investigation of the mechanism of action and vascular effects of VEGF-targeted agents in humans will help to address these questions. Mechanistic studies in humans will be aided by the development and validation of surrogate clinical end points such as noninvasive assessment of hemodynamics and vascular changes within tumors, using imaging studies.
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PMID:Future directions in vascular endothelial growth factor-targeted therapy for metastatic colorectal cancer. 1714 24

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, was approved in 2004 for use in combination with intravenous 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer. Bevacizumab is the first approved agent that targets tumor angiogenesis. The pivotal phase III trial showed significantly greater overall and progression-free survival with the addition of bevacizumab to irinotecan, 5-fluorouracil, and leucovorin. These outcomes were observed irrespective of patients' pretreatment characteristics (age >/=65 years, >/=1 site of metastasis, or location of primary tumor). Furthermore, there was a significant survival benefit regardless of pretreatment biomarkers, including plasma vascular endothelial growth factor level, tumor thrombospondin and p53 expression, and mutational status in k-ras, b-raf, and p53. Analysis of data in responders and nonresponders showed a response-independent survival benefit, indicating that even those in whom there was not an objective tumor response by standard criteria benefited from the addition of bevacizumab. Preliminary data on the addition of bevacizumab to oxaliplatin- and capecitabine-based regimens for the first-line treatment of metastatic colorectal cancer show that these regimens are well tolerated, with consistent increases in objective response rates, time to progression, and overall survival. The survival advantages in patients with metastatic colorectal cancer with the addition of bevacizumab to chemotherapy support the use of this agent in first-line treatment.
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PMID:Bevacizumab in combination with chemotherapy: first-line treatment of patients with metastatic colorectal cancer. 1714 25


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