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

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.

Author information

1
Vanderbilt University Medical Center, Department of Veterans Affairs, Nashville, TN, USA. emily.chan@vanderbilt.edu

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 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.

PMID:
21217396
PMCID:
PMC3133812
DOI:
10.1097/COC.0b013e3181fe46a1
[Indexed for MEDLINE]
Free PMC Article
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