Colorectal cancer (CRC) is a worldwide public health problem, with nearly 
800,000 new cases diagnosed each year, resulting in approximately 500,000 
deaths. When advanced metastatic disease is diagnosed, CRC is associated with a 
poor prognosis, and 5-year survival rates are in the range of 5%-8%. 
Chemotherapy has been the mainstay approach for patients with advanced CRC. For 
nearly 40 years, the main drug used for this disease was the fluoropyrimidine 
5-fluorouracil (5-FU). Significant advances have been made in chemotherapy 
treatment options for patients with metastatic disease, such that improvements 
in 2-year survival are now being reported with median survival rates of 21 
months to 24 months. Over the past 10 years, 3 new cytotoxic chemotherapy agents 
have been approved by the FDA for metastatic CRC. These compounds include the 
topoisomerase I inhibitor irinotecan, the third-generation platinum analogue 
oxaliplatin, and the oral fluoropyrimidine capecitabine. Since 2004, 3 novel 
biologic agents have been approved by the FDA, and they include the 
anti-epidermal growth factor receptor antibodies cetuximab and panitumumab and 
the anti-vascular endothelial growth factor bevacizumab. The oral 
fluoropyrimidine capecitabine has been effectively and safely combined with 
irinotecan (CAPIRI) and/or oxaliplatin (CAPOX). Three randomized phase III 
studies have now shown that CAPOX is equivalent to FOLFOX 
(5-FU/leucovorin/oxaliplatin)-based regimens. Significant interest has centered 
around combining capecitabine-based cytotoxic regimens with the biologic agents, 
and specifically, bevacizumab and cetuximab. This review will update the current 
status of these capecitabine-based combination regimens.