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

Am J Clin Oncol. 2011 Dec;34(6):581-6. doi: 10.1097/COC.0b013e3181fe46a1.


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 loading dose followed by weekly cetuximab at 250 mg/m) and celecoxib (200 mg orally twice daily). Urinary PGE-M, a stable metabolite of PGE2 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Celecoxib
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Cyclooxygenase 2 / metabolism
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Signal Transduction / drug effects*
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 2
  • EGFR protein, human
  • ErbB Receptors
  • Celecoxib
  • Cetuximab