Adjuvant therapy of stage III colon cancer

The decision for adjuvant therapy of colon cancer by both physicians and patients requires many factors, including knowledge of the risk for recurrence (prognosis), the likelihood of significant clinical benefit (prediction), toxicity of treatment, comorbidities, and the patient's understanding and acceptance of both the relative and absolute benefit of therapy. To predict the risk of recurrence, clinicopathologic features have typically been used such as the number of positive and negative nodes, T stage, tumor differentiation, obstruction and lymphovascular invasion. More recent quantitative prognostic markers include microsatellite instability, with MSI-H conferring better prognosis. In addition, in combination with MSI, gene expression profiles have been developed which may be especially helpful in stage II disease, and in some low risk stage III patients to decide on whether they should receive combination chemotherapy, capecitabine or no adjuvant treatment. The standard treatment for most stage III patients is a combination of oxaliplatin with infusional and bolus 5-FU (FOLFOX) or with an oral agent such as capecitabine (XELOX), with equivalent results. Although irinotecan is active in advanced colorectal cancer, two trials of this drug with 5-FU failed to show improvement over the fluoropyrimidines alone. The antiangiogenic agent bevacizumab also failed to improve treatment compared to FOLFOX alone, as did the EGFR agent, cetuximab. Studies are currently underway to compare the standard 6 months of FOLFOX with 3 months of therapy, to reduce the risk of neurotoxocity associate with oxaliplatin, while maintaining treatment efficacy.