Colorectal cancer (CRC) progresses through multiple distinct stages that are potentially amenable to chemopreventative intervention. Epidermal Growth Factor Receptor (EGFR) inhibitors can shrink advanced tumors including CRC. There is significant evidence that EGFR also plays important roles in CRC initiation, and that EGFR inhibitors block tumorigenesis. We therefore performed a double-blind randomized trial (N=45) to test whether the EGFR inhibitor erlotinib (25mg, 50mg and 100mg doses) given for up to 28 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 CRC, and normal rectal tissue. Participants were stratified by NSAID dose. Erlotinib was well tolerated and there were no unanticipated adverse events. Colorectal ACF and normal tissue EGFR signaling changes with erlotinib were modest and there was no clear dose response. However, individuals with high baseline EGFR signaling may potentially constitute a subset that could benefit from this strategy. Overall, our results support the safety of erlotinib in the chemoprevention setting, but efficacy in colorectal EGFR signaling inhibition is likely insufficient to merit further studies without additional pre-screening stratification.

Citation Format: Steven Lipkin, Asmita Bhattacharya, Timothy Morgan, Jason Zell, Daniel Gillen, Vanessa Wong, Jinah Chung, Wen Pin Chen, Rachel Gonzalez, Frank Meyskens, Luz Rodriguez, Eva Szabo, Robert Carroll, Richard Benya. A phase IIa randomized, double-blind trial of erlotinib in inhibiting EGF receptor signaling in aberrant crypt foci of the colon. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr CN07-01.