Introduction: Up-front treatment of metastatic colorectal cancer (mCRC) has progressively become more complex during last few years. Nowadays, treatment options range from monotherapies with biologics or traditional chemotherapeutic agents to intensive combinations of chemotherapy plus targeted drugs.
Areas covered: This review deals with the results of the most recent first-line trials in the medical treatment of mCRC, with a special focus on recently closed or ongoing trials of intensive concomitant combinations of all active cytotoxics plus a biologic agent.
Expert opinion: Combinations of three cytotoxic drugs plus a biologic are under clinical investigation and therefore should not be recommended for routine use, nevertheless preliminary results are promising. The main challenges for the future are not only to demonstrate the real clinical usefulness of intensive approaches, but also to gain the ability of defining prior to treatment which patients will benefit most on the basis of clinical and molecular elements.