The Role of Targeted Therapy in the Treatment of Metastatic Colorectal Cancer

摘要

Colorectal cancer is the fourth most common malignant disease in Korea. Until recently, fluorouracil was the only effective chemotherapeutic agent for colorectal cancer. But during the past decades, the Food and DrugAdministration (FDA) has approved four new drugs for advanced colorectal cancer. Two of them (irinotecan and oxaliplatin) are cytotoxic drugs, whereas the other two (bevacizumab and cetuximab) are monoclonal antibodies against molecular targets. Bevacizumab, a humanized antibody directed against the vascular endothelial growth factor, has been examined in combination with chemotherapeutic agents in several clinical trials in patients with advanced colorectal cancer. According to the phase III randomized controlled clinical trial, the addition of bevacizumab to IFL (irinotecan, 5-FU, leucovorin) led to an impressive, statistically significant increase in the rate of response and prolongation in median overall survival. Recently, a statistically significant prolongation in median survival was also reported with the addition of bevacizumab to FOLFOX4 (oxaliplain, 5-FU, leucovorin) regimen in patients with advanced colorectal cancer. Cetuximab is a monoclonal antibody against the epidermal growth factor receptor. It appears to be synergistic with irinotecan, even in irinotecanrefractory tumors. The most common side effect of cetuximab is acne-like rash, and interestingly, the development and severity of it have been correlated with an increased likelihood of an objective response. In the future, additional research will be required to define the optimal selection and scheduling of available cytotoxic and biologic treatment in individually tailored therapeutic strategies.