TY - JOUR
T1 - Dual blockade of the EGFR and COX-2 pathways
T2 - A phase II trial of cetuximab and celecoxib in patients with chemotherapy refractory metastatic colorectal cancer
AU - Chan, Emily
AU - LaFleur, Bonnie
AU - Rothenberg, Mace L.
AU - Merchant, Nipun
AU - Lockhart, Albert Craig
AU - Trivedi, Bakula
AU - Chung, Christine H.
AU - Coffey, Robert J.
AU - Berlin, Jordan D.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - celecoxib
KW - cetuximab
KW - colorectal cancer
KW - cyclooxygenase-2 pathway
KW - epidermal growth factor receptor pathway
UR - http://www.scopus.com/inward/record.url?scp=81855166671&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81855166671&partnerID=8YFLogxK
U2 - 10.1097/COC.0b013e3181fe46a1
DO - 10.1097/COC.0b013e3181fe46a1
M3 - Article
C2 - 21217396
AN - SCOPUS:81855166671
SN - 0277-3732
VL - 34
SP - 581
EP - 586
JO - American Journal of Clinical Oncology: Cancer Clinical Trials
JF - American Journal of Clinical Oncology: Cancer Clinical Trials
IS - 6
ER -