Summary

Significant advances have been made in the treatment of advanced CRC over the past four to five years.This progress has been made possible with the introduction of three novel cytotoxic agents, capecitabine, irinotecan, and oxaliplatin, and the development of two novel targeted therapies, BV and cetuximab.

During this time period, the median survival of patients with stage IV disease has gone from 10-12 months to nearly 24 months. It is now well-established that all patients with advanced disease should have access to all of these active agents at some point in the course of their treatment.

Despite the development of active combination regimens, however, improvements in the actual cure rate have not yet been achieved.With this in mind, intense efforts have focused on identifying novel targeted therapies that target specific growth factor receptors, critical signal transduction pathways, and/or key pathways that mediate the process of angiogenesis.The recent clinical results with the anti-VEGF antibody, bevacizumab,in combination with the IFL bolus weekly regimen provide important validation for the process of angiogenesis being an important chemotherapeutic target for CRC.Similarly,the randomized Phase II study documenting the clinical activity of the combination of the anti-EGFR antibody cetuximab and irinotecan- based therapy and/or cetuximab monotherapy validate the role of the EGFR-signaling pathway as a key target for chemotherapy.Combination regimens incorporating standard chemotherapy with novel targeted agents with activity in advanced disease are now being evaluated in the adjuvant setting.Investigators continue to focus their efforts on identifying novel therapies that target specific growth factor receptors, critical signal transduction pathways, and/or key pathways that mediate the process of angiogenesis. The goal is to integrate these novel targeted therapies into standard chemotherapy regimens so as to advance the therapeutic options for the treatment of advanced CRC