Sandhya Aggarwal, MD

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Current Therapies for Advanced Colorectal Cancer

April 15th 2005

Significant advances have been made in the treatment of advancedcolorectal cancer over the past 5 years, namely due to the introductionof three novel cytotoxic agents-capecitabine (Xeloda), irinotecan(Camptosar), and oxaliplatin (Eloxatin)-and the recent approval oftwo 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 thattarget 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 antibodybevacizumab can be safely and effectively used in combination witheach of the active anticancer agents used in colorectal cancer. Despitethe development of active combination regimens, significant improvementsin the actual cure rate have not yet been achieved. Combinationregimens with activity in advanced disease are being evaluated in theadjuvant and neoadjuvant settings. The goal is to integrate these targetedstrategies into standard chemotherapy regimens so as to advancethe therapeutic options for the treatment of advanced colorectal cancer.Finally, intense efforts are attempting to identify the critical molecularbiomarkers that can be used to predict for either clinicalresponse to chemotherapy and/or targeted therapies and/or the drugspecificside effects. The goal of such studies is to facilitate the evolutionof empiric chemotherapy to individually tailored treatments forpatients with colorectal cancer.