Colorectal carcinoma is the third most common cancer worldwide. Approximately 25% of patients with colorectal cancer present with overt metastatic disease, and metastatic disease develops in 40 to 50% of newly diagnosed patients .
The overall therapeutic goals for most patients with metastatic colorectal carcinoma (mCRC) are to improve symptoms, control the disease, prolong life span and maximize quality of life, rather than cure. Therefore, the ratio of efficacy to toxicity is one of the most important factors in choosing amongst treatment options and sequencing treatment regimens. In addition, the choice of first line systemic therapy will affect the options for second line treatment. Second line treatment options for patients with mCRC will be based on the treatment received during previous adjuvant treatment, in the first line metastatic setting and will also depend on the molecular profiling of the tumour.
The combination of a fluoropyrimidine (5-fluorouracil [5-FU] or oral capecitabine) with either oxaliplatin or irinotecan has been widely accepted as standard cytotoxic chemotherapy for mCRC, as either first or second line therapy. These regimens consist of folinic acid/5-FU/oxaliplatin (FOLFOX), capecitabine/oxaliplatin (XELOX), folinic acid/5-FU/irinotecan (FOLFIRI), and capecitabine/irinotecan (XELIRI). [2-6]
In addition, biologic agents have been used in combination with the above chemotherapy regimens in mCRC. These include agents that target the vascular endothelial growth factor (VEGF) receptor pathway (bevacizumab and aflibercept) [7-8] or those that target the epidermal growth factor receptor (EGFR) pathway (cetuximab and panitumumab) [9-10] depending on the tumour molecular profile and tumour locality .
As the number of agents has increased, choosing the most effective treatment strategy has become increasingly complex. There is thus a clinical need to tailor treatment to relevant patient groups and tumour subtypes.