Update on clinical data combining capecitabine with targeted agents in newly diagnosed colorectal cancer.

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.