How to integrate biologicals in the continuum of care.

Colorectal cancer is the second most common cancer in Europe and has a worldwide annual incidence of 945,000 [ 1 Boyle P Ferlay J Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005; 16: 481-488 Crossref PubMed Scopus (1124) Google Scholar , 2 Parkin DM Global cancer statistics in the year 2000. Lancet Oncol. 2001; 2: 533-543 Abstract Full Text Full Text PDF PubMed Scopus (2144) Google Scholar ]. The landscape for the management of metastatic colorectal cancer (mCRC) is rapidly changing with development of more effective cytotoxic agents, in tandem with clinical development of biological agents. Progress in the multidisciplinary management of resectable and initially non-resectable mCRC and the combination of cytotoxics (oxaliplatin, irinotecan, capecitabine) with biological agents (bevacizumab, cetuximab and panitumumab) have increased the therapeutic armamentarium for patients with mCRC. Bevacizumab, a humanised monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with fluoropyrimidine-based chemotherapy has been accepted as one of the standard first-line treatments for mCRC. Cetuximab, a chimeric IgG1 monoclonal antibody, and panitumumab, a fully human monoclonal IgG2 antibody targeting epidermal growth factor receptor (EGFR), have shown activity as single agents in chemo refractory patients and in combination, particularly with irinotecan. In light of emerging data, clinicians are faced with major challenges of choosing the best combination of cytotoxics and biologicals, as well as the best sequence and duration of treatment. Better understanding of the molecular mechanisms of resistance to treatment, risks of adverse events and added costs will enable us to individualise and optimise the treatment for these patients.