The Role of Biologicals in the Management of Metastatic Colorectal Cancer (Feature Article: Gastrointestinal Cancer) (Clinical Report‪)‬

The management of patients with metastatic colorectal cancer (CRC) has changed dramatically over the last years with increasing chances of prolonged survival. The median survival of patients with unresectable metastatic disease now approaches 24 months. The development of new cytotoxic and targeted agents, as well as the multidisciplinary management of patients with resectable and initially non-resectable metastases, have contributed to this progress. The development of the cytotoxic agents irinotecan, oxaliplatin and capecitabine and of the biological agents bevacizumab, cetuximab and panitumumab has clearly increased the therapeutic options for patients with metastatic CRC. There are also several other new agents that are also far advanced in development. Resection of liver or lung metastases can lead to cure of patients with metastatic CRC [1, 2]. Complete resection of metastases leads to longterm survival rates of 30-40%. Owing to more active, new combination regimens, some patients with initially unresectable liver metastases can also be downsized to resectable disease, leading to chances for cure in these patients. New, targeted agents have recently been introduced to therapeutic regimens for patients with metastatic CRC. There is a strong preclinical and clinical rationale for the use of vascular endothelial growth factor (VEGF) inhibitors. The anti-VEGF monoclonal antibody, bevacizumab, increases the activity of a variety of active cytotoxic regimens and it has been shown in randomised phase III trials that when combined with irinotecan plus 5-fluorouracil (5-FU)/leucovorin (LV) in the first-line treatment of metastatic CRC and with FOLFOX (5-FU/LV/ oxaliplatin) in second-line treatment, leads to an increased median survival, progression-free survival (PFS) and response rate (RR) compared to the cytotoxic chemotherapy alone [3]. Moreover, it has also been demonstrated in randomised Phase II studies [4], and in a combined analysis of these Phase II studies [5], that bevacizumab increases the activity of 5-FU/LV in first-line treatment of metastatic CRC. A large randomised Phase III study of FOLFOX or capecitabine/oxaliplatin [+ or -] bevacizumab in first-line treatment [6] showed that capecitabine is as effective as intravenous 5-FU/LV when combined with oxaliplatin and that bevacizumab increases the PFS of the fluoropyrimidine/ oxaliplatin combination.