Everolimus in colorectal cancer.

Published

Journal Article (Review)

INTRODUCTION: There has been a strong preclinical rationale for studying mammalian target of rapamycin (mTOR) inhibitors as single agents or in combination, in multiple malignancies and colorectal cancer in particular. AREAS COVERED: The authors summarize the complete clinical experience to date of all trials, both published and in abstract form, of everolimus in colorectal cancer. While initial Phase I trials showed promise, further studies have confirmed that single agent everolimus is not active in advanced metastatic colorectal carcinoma with trials showing single agent tolerability, but without significant hints of efficacy in terms of either objective tumor responses or prolonged stable disease. Combination regimens, including combinations with cytotoxic chemotherapy, and inhibitors of VEGF, EGFR and HDAC have been tested specifically in the colorectal setting in Phase I and Phase II clinical trials. The authors discuss the potential reasons for mixed results and suggest future directions for the development of everolimus in colorectal malignancies. EXPERT OPINION: Studies demonstrate limited clinical activity of everolimus for the treatment of advanced colorectal cancer and have been complicated by increases in toxicity. However, the central role of the PI3K/mTOR pathway in cancer biology suggests that other drug combinations with mTOR inhibition may still merit evaluation.

Full Text

Duke Authors

Cited Authors

  • Altomare, I; Hurwitz, H

Published Date

  • March 2013

Published In

Volume / Issue

  • 14 / 4

Start / End Page

  • 505 - 513

PubMed ID

  • 23406528

Pubmed Central ID

  • 23406528

Electronic International Standard Serial Number (EISSN)

  • 1744-7666

Digital Object Identifier (DOI)

  • 10.1517/14656566.2013.770473

Language

  • eng

Conference Location

  • England