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)

Recent trials have established the IFL combination (fluorouracil [5-FU], leucovorin, and irinotecan [CPT-11, Camptosar]) as a new standard first-line therapy for patients with metastatic colorectal cancer. Median survival for such patients treated with IFL still ranges from approximately 14 to 18 months, however, underscoring the need for new agents with novel mechanisms of action. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumor growth, invasion, and metastasis. A potent stimulus of angiogenesis is vascular endothelial growth factor (VEGF); two agents developed to inhibit VEGF activity, bevacizumab (Avastin) and SU5416, are in advanced clinical trials. Based on encouraging results in phase I and II trials with bevacizumab, a randomized trial of IFL with or without this monoclonal antibody is under way. Similarly, a randomized trial of 5-FU and leucovorin with or without the tyrosine kinase inhibitor SU5416 has recently completed accrual and results are pending. SU5416 is also being tested in a phase I/II trial combined with IFL. This article briefly reviews preclinical and clinical data leading to the current trials of these two agents in patients with colorectal cancer.
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PMID:Targeting vascular endothelial growth factor in colorectal cancer. 1219 27

Angiogenesis is essential for tumor growth and metastasis and is a promising target in the search for new anti-neoplastic agents. Angiogenesis is a tightly regulated process dependent on the complex interplay between inhibitory and stimulatory angiogenic factors. Vascular endothelial growth factor is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against vascular endothelial growth factor, has shown initial preclinical and clinical activity. This review will outline the conceptual basis of anti-angiogenic therapy, discuss the critical role of vascular endothelial growth factor, and summarize the available data on the use of bevacizumab in colorectal cancer.
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PMID:Inhibition of vascular endothelial growth factor in the treatment of colorectal cancer. 1280 94

Bevacizumab, an antivascular endothelial growth factor monoclonal antibody, is being developed by Genentech and Roche as an anti-angiogenesis therapy for the potential treatment of solid tumors. In June 2003, bevacizumab was granted Fast Track status by the FDA for the potential treatment of first-line colorectal cancer. The antibody is currently in phase III trials for non-small-cell lung, colorectal and breast cancers, and in phase II trials for various other solid tumor types.
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PMID:Technology evaluation: bevacizumab, Genentech/Roche. 1475 93

In colorectal cancer, increased expression of the angiogenesis promoter vascular endothelial growth factor correlates with invasiveness, vascular density, metastases, recurrence and prognosis. Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor. In recent clinical trials, bevacizumab has been shown to prolong the time to disease progression and the survival of patients with colorectal cancer. In six patients with adenocarcinoma of the rectum, bevacizumab decreased tumour blood perfusion and volume, interstitial fluid pressure, the number of circulating endothelial cells and fluorodeoxyglucose uptake. Surgical specimens showed a marked response in all six patients with only microscopic disease in five of the patients. These effects of bevacizumab on the vascular biology of tumours probably underlie the progression and survival benefits observed in clinical trials of colorectal cancer.
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PMID:Vascular biology support for the use of bevacizumab in colorectal cancer. 1517 56

Monoclonal antibodies have been developed to target specific proteins involved in the development and progression of cancer. These reagents have the advantage of exquiste specificity, and as currently engineered, low toxicity. The impact monoclonal antibody therapy has recently been demonstrated in colorectal cancer, in which two pathways critical to carcinogenesis have been targeted. The targets are the epidermal growth factor receptor signaling pathway and angiogenesis. Antibodies directed to proteins in both pathways have shown significant activity especially in combination with chemotherapy, and studies in the adjuvant setting are in progress. We review the use of monoclonal antibodies in the treatment of colorectal cancer with particular attention to edrecolomab (Mab 17-1A), bevacizumab (Avastin), cetuximab (IMC-C225), ABX-EGF and EMD 72000. Additional compounds are in earlier stages of development, and the future of this approach in solid tumours is promising.
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PMID:Monoclonal antibodies in the treatment of colorectal cancer. 1517 87

Advanced colorectal cancer remains an urgent health concern, despite improvements in systemic chemotherapy. Targeted therapeutics promise effective tumor therapy with minimal side effects. Angiogenesis (the formation of new blood vessels) is essential for tumor growth and metastasis and may be an ideal target in the search for new antineoplastic agents. Vascular endothelial growth factor is one of the best characterized of the proangiogenic growth factors that regulate angiogenesis and is a logical target in colorectal cancer therapy. Bevacizumab (Avastin; Genentech Inc.; South San Francisco, CA), a humanized murine monoclonal antibody directed at vascular endothelial growth factor, is being evaluated in the treatment of various types of cancer. It has shown promising efficacy in phase II clinical trials in patients with metastatic colorectal cancer. Addition of bevacizumab at a dose of 5 mg/kg to chemotherapy (5-fluorouracil plus leucovorin) resulted in a higher objective response rate (40% versus 17%), longer time to disease progression (9.0 versus 5.2 months), and longer median survival time (21.5 versus 13.8 months). Hypertension and thrombosis were the principal safety concerns, but were manageable. Further phase II/III studies of bevacizumab, administered with 5-fluorouracil plus leucovorin, with or without irinotecan and/or oxaliplatin, in colorectal cancer, are under way.
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PMID:Targeted therapy of colorectal cancer: clinical experience with bevacizumab. 1517 11

Bevacizumab (Avastin; Genentech, Inc.; South San Francisco, CA) is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, a key regulator of tumor angiogenesis. Bevacizumab demonstrated potent antitumor activity in preclinical models and has also shown biologic activity and clinical benefit in clinical studies. Notably, a randomized, placebo-controlled phase II trial in renal cell carcinoma demonstrated a significantly longer time to tumor progression with bevacizumab monotherapy. Furthermore, in a phase III trial for untreated advanced colorectal cancer, the addition of bevacizumab to chemotherapy led to significantly longer overall survival and progression-free survival times than chemotherapy alone. The clinical development of bevacizumab has been expanded to include confirmatory phase III trials and exploratory phase II trials in a variety of solid tumors and hematologic malignancies. Treatment regimens being examined include bevacizumab alone and in combination with conventional chemotherapy, radiation, immune therapy, and biologically targeted agents.
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PMID:Expanding the clinical development of bevacizumab. 1517 13

Colorectal cancer remains one of the major causes of cancer death worldwide, but the past few years have witnessed the development of a number of new, effective treatment options, which have led to considerable improvement in the survival rate for patients suffering from this common cancer. The advent of agents such as capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin (Eloxatin), and newer molecular targeted agents such as cetuximab (Erbitux) and bevacizumab (Avastin) brought innovation to the treatment of colorectal cancer. Oncologists are no longer restricted to using fluorouracil and its variations as the only active treatment, and the number of patients who are able to live longer continues to increase. Patients presenting with stage III cancer can expect a greater chance for cure, and those presenting with metastatic disease can expect a median survival approaching 2 years.
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PMID:Progress in the development of novel treatments for colorectal cancer. 1521 91

The treatment of colorectal cancer has undergone enormous changes in the past decade. From a disease with a single treatment option (ie, fluorouracil, a modestly effective drug), the treatment options have evolved to include at least five new classes of antineoplastic agents. Among the considerable number of recently approved drugs, two are monoclonal antibodies and are the testing ground for our rapidly emerging knowledge about cancer cell biology. Cetuximab (Erbitux) targets the epidermal growth factor receptor, an important molecule involved with cell cycling, survival, invasion, and metastasis. Bevacizumab (Avastin) neutralizes the vascular endothelial growth factor, blocking its ability to activate its receptor on the endothelial cells. The development of both antibodies resulted from decades of research in molecular and cell biology, as well as preclinical and clinical studies, and signals a new paradigm where the tumor cells' own unique features are exploited in a rational way.
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PMID:Monoclonal antibodies: the foundation of therapy for colorectal cancer in the 21st century? 1521 93

Adjuvant therapy with chemotherapy and/or radiation therapy in addition to surgery improves outcome for patients with high-risk carcinomas of the colon or rectum. For colon cancer, fluorouracil (5-FU) combined with leucovorin is a current standard of care that improves long-term survival. A recent European trial (MOSAIC) has documented significant improvement in 3-year disease-free survival when oxaliplatin (Eloxatin) was added to infusional 5-FU and leucovorin in the FOLFOX regimen. Two US cooperative group trials will evaluate the addition of antiangiogenesis therapy with bevacizumab (Avastin) to chemotherapy. A third trial will evaluate FOLFOX, irinotecan (Camptosar) combined with infusional 5-FU and leucovorin (FOLFIRI), and the sequential use of FOLFOX followed by FOLFIRI. In rectal cancer, postoperative 5-FU-based chemotherapy combined with irradiation can improve both local tumor control and survival. The German Rectal Cancer Group has recently reported that preoperative combined-modality therapy is less toxic and more effective in preventing local tumor relapse compared to similar treatment given postoperatively. A coordinated pair of cooperative group clinical trials will evaluate oral capecitabine (Xeloda) as a radiation enhancer in the preoperative setting, and the FOLFOX and FOLFIRI regimens compared to 5-FU and leucovorin following surgery. Predictive and prognostic molecular markers will be studied in these new adjuvant therapy clinical trials for both colon and rectal cancer with the goal of developing future regimens tailored to individual patients. There has been a recent and dramatic increase in the pace of drug development for colorectal cancer which holds promise to further improve curative therapy as part of a multidisciplinary approach in the surgical adjuvant setting.
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PMID:Current status of adjuvant therapy for colorectal cancer. 1521 94


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