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Clin Colorectal Cancer. 2012 Mar;11(1):1-13. doi: 10.1016/j.clcc.2011.05.005. Epub 2011 Jul 12.

An update on the current and emerging targeted agents in metastatic colorectal cancer.

Author information

1
Division of Hematology-Oncology, Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA, USA. chueyale@yahoo.com

Abstract

Over the past 8 to 10 years, significant advances have been made in the treatment of metastatic colorectal cancer (mCRC). In particular, the development of the targeted biologic agents bevacizumab, cetuximab, and panitumumab, and their integration with cytotoxic chemotherapy regimens has led to improvements in clinical efficacy. Despite these gains, the overall impact of current targeted agents in the treatment of mCRC has been relatively modest, and while 2-year survival has improved, no gains have been made, as of yet, in 5-year survival. Intense efforts continue to be focused on developing novel targeted agents with a different spectrum of activity. Presently, five novel targeted molecules are in phase III trials, including the antiangiogenesis agents aflibercept and ramucirumab, two novel receptor tyrosine kinase inhibitors, regorafenib and brivanib, and the Akt inhibitor perifosine. There are an additional 52 phase II trials investigating a wide range of other candidate molecules. The potential list of approved targeted agents in mCRC seems likely to increase over the next 5 to 10 years. To maximize their potential clinical impact, however, it will be critically important to introduce efficient molecular diagnostic methodologies into the drug development process for the identification and validation of predictive biomarkers for chemosensitivity. This article reviews the development of targeted agents for the treatment of mCRC, including the three molecules currently approved by the US Food and Drug Administration (FDA), as well as the main non-FDA-approved therapeutics currently undergoing phase II and III clinical testing.

PMID:
21752724
DOI:
10.1016/j.clcc.2011.05.005
[Indexed for MEDLINE]

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