TY - JOUR
T1 - Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma
T2 - Results of a phase II trial
AU - Dragovich, Tomislav
AU - Burris, Howard
AU - Loehrer, Patrick
AU - Von Hoff, Daniel D.
AU - Chow, Sherry
AU - Stratton, Steven
AU - Green, Sylvan
AU - Obregon, Yrma
AU - Alvarez, Irene
AU - Gordon, Michael
PY - 2008/4
Y1 - 2008/4
N2 - OBJECTIVES: Cycloxygenase-2 (COX-2) is overexpressed in pancreatic tumors where it may be involved in inflammation, carcinogenesis, and the regulation of neoangiogenesis. The purpose of this trial was to evaluate the combination of intravenous gemcitabine with selective COX-2 inhibitor, celecoxib for effect on survival, disease progression, and tolerability in patients with advanced pancreatic cancer. In addition, limited pharmacokinetic and pharmacodynamic analyses were preformed. MATERIALS AND METHODS: Eligible patients included those with locally advanced or metastatic pancreatic cancer with no prior chemotherapy and ECOG performance status 0-2. The treatment consisted of intravenous gemcitabine 1000 mg/m weekly × 7 weeks and concurrent daily oral celecoxib 400 mg orally twice a day. Daily oral low-dose aspirin 81 mg was administered throughout the study as a precaution for increased risk of thrombotic events. Those with stable or responsive disease were continued on intravenous gemcitabine 1000 mg/m weekly × 3 weeks and concurrent oral celecoxib. RESULTS: Twenty five patients have been enrolled at 3 centers. Five patients had locally advanced cancer; 20 had metastatic disease. The most common grade 3/4 hematological toxicities were neutropenia (32%) and anemia (20%). Four patients (17%) had partial response and 7 (35%) demonstrated stable disease. The estimated 12-month survival rate was 15%, which did not reach the predetermined efficacy end point. There was a trend suggestive of correlation between a decrease in serum vascular endothelial growth factor and patient survival. CONCLUSION: The addition of celecoxib to gemcitabine therapy did not demonstrate significant improvement in measured clinical outcomes, in patients with advanced pancreatic cancer. Higher doses of celecoxib may be needed to observe significant antitumor activity.
AB - OBJECTIVES: Cycloxygenase-2 (COX-2) is overexpressed in pancreatic tumors where it may be involved in inflammation, carcinogenesis, and the regulation of neoangiogenesis. The purpose of this trial was to evaluate the combination of intravenous gemcitabine with selective COX-2 inhibitor, celecoxib for effect on survival, disease progression, and tolerability in patients with advanced pancreatic cancer. In addition, limited pharmacokinetic and pharmacodynamic analyses were preformed. MATERIALS AND METHODS: Eligible patients included those with locally advanced or metastatic pancreatic cancer with no prior chemotherapy and ECOG performance status 0-2. The treatment consisted of intravenous gemcitabine 1000 mg/m weekly × 7 weeks and concurrent daily oral celecoxib 400 mg orally twice a day. Daily oral low-dose aspirin 81 mg was administered throughout the study as a precaution for increased risk of thrombotic events. Those with stable or responsive disease were continued on intravenous gemcitabine 1000 mg/m weekly × 3 weeks and concurrent oral celecoxib. RESULTS: Twenty five patients have been enrolled at 3 centers. Five patients had locally advanced cancer; 20 had metastatic disease. The most common grade 3/4 hematological toxicities were neutropenia (32%) and anemia (20%). Four patients (17%) had partial response and 7 (35%) demonstrated stable disease. The estimated 12-month survival rate was 15%, which did not reach the predetermined efficacy end point. There was a trend suggestive of correlation between a decrease in serum vascular endothelial growth factor and patient survival. CONCLUSION: The addition of celecoxib to gemcitabine therapy did not demonstrate significant improvement in measured clinical outcomes, in patients with advanced pancreatic cancer. Higher doses of celecoxib may be needed to observe significant antitumor activity.
KW - COX-2 (cycloxygenase-2)
KW - Celecoxib
KW - Gemcitabine
KW - Pancreatic adenocarcinoma
KW - Phase II trial
KW - VEGF (vascular endothelial growth factor)
UR - http://www.scopus.com/inward/record.url?scp=42049123958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42049123958&partnerID=8YFLogxK
U2 - 10.1097/COC.0b013e31815878c9
DO - 10.1097/COC.0b013e31815878c9
M3 - Article
C2 - 18391600
AN - SCOPUS:42049123958
VL - 31
SP - 157
EP - 162
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
IS - 2
ER -