Chemotherapy for colorectal cancer in the metastatic and adjuvant setting: past, present and future

There have been significant advances in the use of chemotherapy in the treatment of colorectal cancer patients over the last 20 years. Initial improvements in treatment were made with increased understanding of the pharmacology of 5-fluorouracil and the discovery of modulators of its activity (e.g., leucovorin). However, in the last few years the discovery of new cytotoxic drugs with efficacy in large bowel cancer (e.g., oxaliplatin and irinotecan) and monoclonal antibodies (e.g., bevacizumab and cetuximab) have significantly improved patient outcome and prognosis. Systemic chemotherapy in the metastatic setting has been shown to prolong survival and improve quality of life. Chemotherapy now also has a clear role as an adjunct to surgery to improve survival in stage III and certain 'high-risk' stage II colorectal cancer patients. The evolution of chemotherapy use, current practice in the metastatic and adjuvant setting and possible future directions are discussed.