While surgery is the cornerstone treatment for early-stage
colorectal cancer,
chemotherapy is the first treatment option for metastatic disease when
tumor lesions are frequently not fully resectable at presentation. Mortality from
colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and
tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic
colorectal cancer is a global treatment strategy, which applies several lines of
therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of
cancer treatment is based on the evaluation of prognostic factors for survival (serum
lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat
sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic
colorectal cancer are
chemotherapy (fluoropyrimidine,
oxaliplatin,
irinotecan), anti-angiogenic agents (e.g.
bevacizumab), and anti-
epidermal growth factor agents (
cetuximab,
panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials.