From chemotherapy to targeted therapy in adjuvant treatment for stage III colon cancer.

Colorectal cancer represents a major public health problem due to its frequency and mortality rate. Adjuvant chemotherapy has improved the prognosis of colon cancer. Six months of oxaliplatin and fluoropyrimidine in combination is the standard adjuvant treatment in stage III patients. Ongoing trials are evaluating the optimal duration of chemotherapy. A critical issue, which needs to be specifically addressed, is the role of adjuvant therapy in elderly patients. Preliminary results of trials evaluating targeted therapies in combination with chemotherapy have shown disappointing results. The monoclonal antibodies bevacizumab, targeting vascular endothelial growth factor (VEGF) and cetuximab, targeting epidermal growth factor receptor (EGFR)/HER1, which improved survival in patients with metastatic colorectal cancer, could even induce chemotherapy resistance in a significant number of patients in the adjuvant setting. A major challenge is emerging to understand the mechanism leading to this effect and to multi-target the tumor cell proliferation and survival network. Clarity regarding the clinical signal needed before launching a phase III study and optimized designs adapted to multiple agents are urgently needed for new trials.