A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum

Daniel L. Gillen, Frank L. Meyskens, Timothy R. Morgan, Jason A. Zell, Robert Carroll, Richard Benya, Wen Pin Chen, Allen Mo, Chris Tucker, Asmita Bhattacharya, Zhiliang Huang, Myra Arcilla, Vanessa Wong, Jinah Chung, Rachel Gonzalez, Luz Maria Rodriguez, Eva Szabo, Daniel W. Rosenberg, Steven M. Lipkin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Colorectal cancer progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal growth factor receptor (EGFR) inhibitors are efficacious in advanced tumors including colorectal cancer. There is significant evidence that EGFR also plays important roles in colorectal cancer initiation, and that EGFR inhibitors block tumorigenesis. We performed a double-blind randomized clinical trial to test whether the EGFR inhibitor erlotinib given for up to 30 days had an acceptable safety and efficacy profile to reduce EGFR signaling biomarkers in colorectal aberrant crypt foci (ACF), a subset of which progress to colorectal cancer, and normal rectal tissue. A total of 45 patients were randomized to one of three erlotinib doses (25, 50, and 100 mg) with randomization stratified by nonsteroidal anti-inflammatory drug (NSAID) use. There were no unanticipated adverse events with erlotinib therapy. Erlotinib was detected in both normal rectal mucosa and ACFs. Colorectal ACF phosphorylated ERK (pERK), phosphorylated EGFR (pEGFR), and total EGFR signaling changes from baseline were modest and there was no dose response. Overall, this trial did not meet is primary efficacy endpoint. Colorectal EGFR signaling inhibition by erlotinib is therefore likely insufficient to merit further studies without additional prescreening stratification or potentially longer duration of use.

Original languageEnglish
Pages (from-to)222-230
Number of pages9
JournalCancer Prevention Research
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Dive into the research topics of 'A phase IIa randomized, double-blind trial of erlotinib in inhibiting epidermal growth factor receptor signaling in aberrant crypt foci of the colorectum'. Together they form a unique fingerprint.

Cite this