Assessing the role of combination therapy in mCRC

Doublet chemotherapy regimens (i.e. FOLFOX and FOLFIRI) have been shown to improve objective response rate and progression-free survival compared with fluoropyrimidine monotherapy, and may also improve overall survival (OS) in patients with metastatic colorectal carcinoma (mCRC). Further improvements in efficacy parameters can be achieved by the addition of a third cytotoxic agent, such as in FOLFOXIRI, or a targeted agent (e.g. bevacizumab or cetuximab) to doublet chemotherapy. Data suggests that two groups of patients, defined by clinical characteristics, may be particularly appropriate for aggressive combination treatment: patients at risk of rapid disease progression, and those with liver metastases, which may become resectable following such therapy. Furthermore, theoretical considerations suggest that use of combination regimens first-line increases the number of patients who are able to benefit from exposure to multiple agents, enabling improvement of overall survival for all patient groups. First-line combination therapy can be envisaged as the first phase in a programme of treatment consisting of intensive induction therapy given for a limited period, followed by less intensive maintenance therapy given until disease progression. On disease progression, intensive therapy with either the induction regimen or another regimen may be considered to regain disease control. While accumulating data have established the efficacy of aggressive induction therapy, further research is required to determine the value and feasibility of maintenance therapy and post-progression reinduction therapy, together with the identification of the most appropriate agents to use in these settings. (C) 2008 Elsevier Ltd. All rights reserved.