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

Overview

MeSH

  • Case-Control Studies
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Signal Transduction

MeSH Major

  • Aberrant Crypt Foci
  • Colorectal Neoplasms
  • Erlotinib Hydrochloride
  • Protein Kinase Inhibitors
  • Receptor, Epidermal Growth Factor
  • Rectum

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. ©2015 American Association for Cancer Research.

publication date

  • March 2015

has subject area

  • Aberrant Crypt Foci
  • Case-Control Studies
  • Colorectal Neoplasms
  • Double-Blind Method
  • Erlotinib Hydrochloride
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Protein Kinase Inhibitors
  • Receptor, Epidermal Growth Factor
  • Rectum
  • Signal Transduction

Research

keywords

  • Clinical Trial, Phase II
  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial

Identity

Language

  • eng

PubMed Central ID

  • PMC4355051

Digital Object Identifier (DOI)

  • 10.1158/1940-6207.CAPR-14-0148

PubMed ID

  • 25604134

Additional Document Info

start page

  • 222

end page

  • 230

volume

  • 8

number

  • 3