Clinical colorectal cancer
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Clin Colorectal Cancer · Dec 2007
ReviewUpdate on clinical data combining capecitabine with targeted agents in newly diagnosed colorectal cancer.
Colorectal cancer (CRC) is a worldwide public health problem, with nearly 800,000 new cases diagnosed each year, resulting in approximately 500,000 deaths. When advanced metastatic disease is diagnosed, CRC is associated with a poor prognosis, and 5-year survival rates are in the range of 5%-8%. Chemotherapy has been the mainstay approach for patients with advanced CRC. ⋯ Three randomized phase III studies have now shown that CAPOX is equivalent to FOLFOX (5-FU/leucovorin/oxaliplatin)-based regimens. Significant interest has centered around combining capecitabine-based cytotoxic regimens with the biologic agents, and specifically, bevacizumab and cetuximab. This review will update the current status of these capecitabine-based combination regimens.
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Clin Colorectal Cancer · Dec 2007
ReviewA retrospective on the inhibition of epidermal growth factor receptor as a therapeutic strategy for patients with relapsed metastatic colorectal cancer: impact on treatment of today's patients.
The epidermal growth factor receptor (EGFR) pathway is overexpressed in many colorectal cancers (CRCs) and is associated with a worse prognosis compared with tumors that do not express EGFR. The development of monoclonal antibodies against this receptor, including cetuximab and panitumumab, and small-molecule inhibitors against the tyrosine kinase protein has led to new therapeutic paradigms in the treatment of metastatic CRC (mCRC). ⋯ Clinical trials with tyrosine kinase inhibitors have yielded disappointing results. This article reviews the clinical trial evidence for treatment strategies based on EGFR inhibition in relapsed/refractory mCRC, mechanisms of resistance to EGFR agents, clinical uncertainties, and future directions.
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Clin Colorectal Cancer · Oct 2007
ReviewFirst-line use of anti-epidermal growth factor receptor monoclonal antibodies in metastatic colorectal cancer.
Several molecular pathways have been shown to play key roles in the development and progression of colorectal cancer (CRC). This enhanced understanding of tumor biology has provided the rationale for the design and development of novel agents that are directed against important targets, including growth factors, receptors, and tumor-specific/tumor-selective antigens. The epidermal growth factor receptor (EGFR) signaling pathway has received much attention over the past 5-10 years because it is overexpressed in more than 85% of tumors from patients with metastatic CRC. ⋯ The clinical studies conducted to date suggest that cetuximab can be safely and effectively combined with oxaliplatin- and irinotecan-based chemotherapy in the first-line treatment of metastatic CRC. Moreover, the results of the CRYSTAL phase III study provide support for the use of the combination of FOLFIRI (5-fluorouracil/leucovorin/irinotecan) and cetuximab in the neoadjuvant setting and allow for R0 surgical resection with curative intent. Much work continues to investigate the critical molecular biomarkers that can be used to predict clinical response to chemotherapy and/or targeted therapies as well as to identify which patients might be at increased risk for developing drug-specific side effects.
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Clin Colorectal Cancer · Oct 2007
ReviewThe role of epidermal growth factor receptor-targeted antibody therapy in previously treated colorectal cancer.
In recent years, increasing amounts of trial data have become available indicating the clinical efficacy of epidermal growth factor receptor (EGFR)-targeted antibody therapy in the management of advanced colorectal cancer (CRC). These trial data have consistently demonstrated the modest single-agent activity of these agents when given in the chemorefractory setting and the potential ability for EGFR-targeted agents to reverse chemoresistance when given in combination with cytotoxic chemotherapy agents. In this article, we review the clinical development of EGFR-targeted therapies and discuss their current role in the management of patients with previously treated advanced CRC.
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Clin Colorectal Cancer · Oct 2007
Optimizing administration of epidermal growth factor receptor-targeted agents in the treatment of colorectal cancer.
The monoclonal antibodies against the epidermal growth factor receptor (EGFR) are active in patients with metastatic colorectal cancer (CRC; mCRC). This activity has been shown initially in irinotecan- and chemotherapy-refractory mCRC. ⋯ However, many unresolved challenges remain regarding this question. New challenges include the development of the most optimal schedule of the EGFR inhibitors and the evaluation of their role in less advanced stages and in the preoperative treatment of liver metastases of CRC.