| In recent years, new anti-cancer and molecular targeted agents has been introduced clinically against unresectable advanced or recurrent (metastatic) colorectal cancer (mCRC). The treatment outcome of mCRC has been much improved. Cytotoxic agents: 5FU+leucovorin, irinotecan (approved in 1995 in Japan), oxaliplatin (approved in 2005), and TAS-102 (approved in 2014) and molecular targeted agents: bevacizumab (approved in 2007) as an anti-vascular endothelial growth factor, (anti-VEGF) antibody (Ab), cetuximab (approved in 2008) or panitumumab (approved in 2010) for RAS wild type mCRC as anti-epithelial growth factor receptor (anti-EGFR) Ab, regorafenib (approved in 2013) as multi-kinase inhibitor, ramucirumab (approved in 2016) as anti-VEGF receptor 2 (anti-VEGFR2) Ab, and aflibercept (approved in 2017) as a newly developed anti-VEGF agent were lined up in mCRC therapy as a single agent or in combination therapy. More recently, immune checkpoint inhibitor (pembrolizumab or nivolumab) have reported promising efficacy for high microsatellite instability (MSI-H) mCRC. Current first line phase III trials of combination regimens (doublet of FOLFRI or FOLFOX plus one of Abs in molecular targeted agents) in mCRC have demonstrated substantial improvements of approximate 30 months on median survival time. Furthermore, curative resection (so-called conversion therapy) of liver-limited metastases following the administration of such effective chemotherapy should substantially improve long-term outcomes. By continued advances in pharmaceutical development combined with appropriate curative resection of organ metastases, we hope that further improvement of survival on mCRC may be amplified and extended. |
