Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma: Results of a phase II trial

Tomislav Dragovich, Howard Burris, Patrick Loehrer, Daniel D. Von Hoff, Hsiao-Hui Chow, Steven P Stratton, Sylvan Green, Yrma Obregon, Irene Alvarez, Michael Gordon

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)157-162
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume31
Issue number2
DOIs
StatePublished - Apr 2008

Fingerprint

Celecoxib
gemcitabine
Adenocarcinoma
Pancreatic Neoplasms
Survival
Neutropenia
Vascular Endothelial Growth Factor A
Aspirin
Disease Progression
Anemia
Neoplasms
Carcinogenesis

Keywords

  • Celecoxib
  • COX-2 (cycloxygenase-2)
  • Gemcitabine
  • Pancreatic adenocarcinoma
  • Phase II trial
  • VEGF (vascular endothelial growth factor)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma : Results of a phase II trial. / Dragovich, Tomislav; Burris, Howard; Loehrer, Patrick; Von Hoff, Daniel D.; Chow, Hsiao-Hui; Stratton, Steven P; Green, Sylvan; Obregon, Yrma; Alvarez, Irene; Gordon, Michael.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 31, No. 2, 04.2008, p. 157-162.

Research output: Contribution to journalArticle

Dragovich, Tomislav ; Burris, Howard ; Loehrer, Patrick ; Von Hoff, Daniel D. ; Chow, Hsiao-Hui ; Stratton, Steven P ; Green, Sylvan ; Obregon, Yrma ; Alvarez, Irene ; Gordon, Michael. / Gemcitabine plus celecoxib in patients with advanced or metastatic pancreatic adenocarcinoma : Results of a phase II trial. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2008 ; Vol. 31, No. 2. pp. 157-162.
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abstract = "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.",
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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, Hsiao-Hui

AU - Stratton, Steven P

AU - Green, Sylvan

AU - Obregon, Yrma

AU - Alvarez, Irene

AU - Gordon, Michael

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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.

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KW - COX-2 (cycloxygenase-2)

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KW - Pancreatic adenocarcinoma

KW - Phase II trial

KW - VEGF (vascular endothelial growth factor)

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