How to integrate molecular targeted agents in the continuum of care.

Molecular targeted agents have enriched the therapeutic options. The VEGF inhibitor Bevacizumab has no single agent activity. It was studied in several phase III chemotherapy trials. The best results were achieved when bevacizumab was combined with fluoropyrimidies (infusional 5-FU and capecitabine) alone or with IFL (bolus 5-FU), while randomized data for the infusional schedule FOLFIRI is missing and data on FOLFOX is negative. The EGF receptor antibodies cetuximab or panitumumab have single agent activity but are only active in k-ras wt tumors. In combination with FOLFIRI or FOLFOX they can improve RR, PFS and OS according to randomized trials. For the use of targeted agents clinicians have to determine the treatment strategy. If cure is the aim or a rapid relieve of tumor related symptoms in aggressive tumors is necessary regimens inducing a high RR such as FOLFOXIRI or FOLFOX / FOLFIRI plus an EGFR antibody are optimal. The treatment of patients with a slow tumor progression or a low tumor burden may start with 5-FU or capecitabine alone of in combination with bevacizumab. According to recently published data of the CRYSTAL study FOLFIRI plus cetuxcimab is also an options in k-ras wt tumors as this is the only regimen that prolongs survival statistically significant and clinically relevant. FOLFOX should not be combined with an EGFR antibody in k-ras mut tumors and combinations of EGFR and VEGF antibodies in combinations with chemotherapy should be avoided outside a clinical trial, as inferior outcomes have been observed.