Dual blockade of the EGFR and COX-2 pathways: A phase II trial of cetuximab and celecoxib in patients with chemotherapy refractory metastatic colorectal cancer

Emily Chan, Bonnie LaFleur, Mace L. Rothenberg, Nipun Merchant, Albert Craig Lockhart, Bakula Trivedi, Christine H. Chung, Robert J. Coffey, Jordan D. Berlin

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) pathways play key and often complementary roles in the pathogenesis of colorectal cancer (CRC). This study explores the clinical and biological effects of combined blockade of these pathways. Methods: Cetuximab-naive patients with refractory CRC were treated with cetuximab (400 mg/m 2 loading dose followed by weekly cetuximab at 250 mg/m 2) and celecoxib (200 mg orally twice daily). Urinary PGE-M, a stable metabolite of PGE 2 that correlates with in vivo COX-2 activity, and serum TGF-α, a ligand that binds to EGFR, were measured serially to assess the biological effect of COX-2 and EGFR blockade. Results: Seventeen patients accrued in this study. Of the 13 patients evaluable for response, 2 (15.4%) had confirmed partial responses, 4 (30.8%) had stable disease, and 7 (53.8%) had progressive disease. The median progression-free survival for all evaluable patients was 55 days (95% confidence interval, 45-112; range, 10-295 d). This study was terminated early owing to lack of sufficient clinical activity. There were no statistically significant differences in serum TGF-α or urinary PGE-M between cycles in responders or nonresponders. Conclusions: This regimen resulted in response rates similar to those published for cetuximab monotherapy in patients with recurrent CRC. Apart from a higher than expected rate of infusion reactions, no other unexpected toxicities were observed. No differences in serum TGF-α or urinary PGE-M between cycles were seen, suggesting that the appropriate targets may not have been hit.

Original languageEnglish (US)
Pages (from-to)581-586
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume34
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • celecoxib
  • cetuximab
  • colorectal cancer
  • cyclooxygenase-2 pathway
  • epidermal growth factor receptor pathway

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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