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.

Chan E, Lafleur B, Rothenberg ML, Merchant N, Lockhart AC, Trivedi B, Chung CH, Coffey RJ, Berlin JD
Am J Clin Oncol. 2011 34 (6): 581-6

PMID: 21217396 · PMCID: PMC3133812 · 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.

MeSH Terms (21)

Animals Antibodies, Monoclonal Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols Celecoxib Cetuximab Colorectal Neoplasms Cyclooxygenase 2 Disease-Free Survival ErbB Receptors Female Humans Male Mice Mice, Nude Neoplasm Metastasis Neoplasm Staging Pyrazoles Signal Transduction Sulfonamides Xenograft Model Antitumor Assays

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