Abstract
In the past decade the median duration of survival with advanced colorectal cancer has increased from 12 months to nearly 24 months. Oxaliplatin and irinotecan are widely used in combination with 5-FU and leucovorin as FOLFOX (FU/LV+oxaliplatin) therapy or FOLFIRI (FU/LV+CPT-11) therapy. Recently two monoclonal antibodies showed significant activity for advanced colorectal cancer. Cetuximab is a chimeric Ig G1 monoclonal antibody that binds to EGFR. Cetuximab has significant activity when given in combination with CPT-11 or FOLFOX (FU/LV+oxaliplatin) chemotherapy.
Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Administration of Bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression. Bevacizumab also had significant activity Combined with FL (FU/LV), IFL (CPT/FU/LV) and FOLFOX (Oxal/FU/LV). These molecular target agents are going to the mainstay of the new era of cancer treatments.
