| Theme |
The State of the Art in Chemotherapy for Gastrointestinal Cancer |
| Title |
Targeted Therapeutics for Patients with Colorectal Cancer |
| Author |
Fumio Nagashima |
Division of Medical Oncology, Internal Medicine, Kyorin University |
| Author |
Satoru Hirokawa |
Division of Medical Oncology, Internal Medicine, Kyorin University |
| Author |
Hiroshi Kitamura |
Division of Medical Oncology, Internal Medicine, Kyorin University |
| Author |
Junji Furuse |
Division of Medical Oncology, Internal Medicine, Kyorin University |
| [ Summary ] |
Cytotoxic chemotherapeutic agents for metastatic colorectal cancer (mCRC) include fluorouracil with leucovorin and irinotecan or oxaliplatin. Clinical studies have shown that epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are valid therapeutic targets for patients with mCRC. Bevacizumab is a humanized IgG1 mAb which disrupts interactions with VEGFRs. The activity of bevacizumab in combination with conventional chemotherapy has been shown in pivotal clinical studies. The NO16966 trial investigated the effectiveness of bevacizumab in combination with FOLFOX／XELOX. The BRiTE trial indicated that continuation of bevacizumab therapy, bevacizumab for maintenance, benefited patients with mCRC. Cetuximab is a chimeric human-murine IgG1 mAb, which binds specifically to the extracellular domain of EGFR. The CRYSTAL trial investigated the effectiveness of cetuximab in combination with FOLFIRI. Significant improvement was evident in median progression-free survival and response rates. Panitumumab is a fully human recombinant IgG2 mAb which binds specifically to the extracellular domain of EGFR. Patients with activating mutations in K-Ras received little or no benefit from anti-EGFR therapy. Future studies of pharmacogenomics may identify new markers for targeted therapeutics, and create new treatment options. |