New Trend in Chemotherapy for Colorectal Cancer

ABSTRACT

5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil. Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. Several molecular targeting agents such as EGFR inhibitors and antiangiogenic agents have developed. Cetuximab induces a broad range of cellular responses in tumors expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. A key angiogenic pathway in the stimulation of tumour growth is the vascular endothelial growth factor (VEGF) pathway, inhibited by the monoclonal antibody bevacizumab. Phase II first line and phase III second line studies of oxaliplatin in combination with bevacizumab are now in progress. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.