Cytotoxic chemotherapy for advanced, non-resectable colorectal cancer

The past decade has seen a step-change in the treatment of advanced, inoperable colorectal cancer. The choice of fluoropyrimidine extends beyond 5-FU to orally available analogues, which have been shown to be equivalent in activity to intravenous 5-FU. The emergence of two additional active chemotherapy agents, irinotecan and oxaliplatin, has improved prognosis of these patients by providing additional lines of therapy. However, this has resulted in an increasing number of regimens, combinations and sequences available to clinicians and patients. In this review we summarise the evidence supporting the use of all active chemotherapy agents, as appropriate, to improve the survival of patients with mCRC, with particular attention to mature phase III trials. The role of novel biological therapies is reviewed elsewhere and will not be covered. Ultimately, the choice of regimen and sequence will depend on patient-specific factors, patient and clinician choice, volume of disease, aims of therapy and, in time, biological markers which may predict for response to a particular drug of combination.