The potential predictive value of cyclooxygenase-2 expression and increased risk of gastrointestinal hemorrhage in advanced non-small cell lung cancer patients treated with erlotinib and celecoxib

Mary Jo Fidler, Athanassios Argiris, Jyoti D. Patel, David H. Johnson, Alan Sandler, Victoria M. Villaflor, John Coon IV, Lela Buckingham, Kelly Kaiser, Sanjib Basu, Philip Bonomi

Research output: Contribution to journalArticle

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Abstract

Purpose: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non - small cell lung cancer (NSCLC). With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC. Experimental Design: Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry. Results: Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21 patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P = 0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers. Conclusions: The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.

Original languageEnglish (US)
Pages (from-to)2088-2094
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number7
DOIs
StatePublished - Apr 1 2008

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Celecoxib
Gastrointestinal Hemorrhage
Cyclooxygenase 2
Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Cyclooxygenase 2 Inhibitors
Peptic Ulcer
Disease-Free Survival
Hemorrhage
Immunohistochemistry
Erlotinib Hydrochloride

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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The potential predictive value of cyclooxygenase-2 expression and increased risk of gastrointestinal hemorrhage in advanced non-small cell lung cancer patients treated with erlotinib and celecoxib. / Fidler, Mary Jo; Argiris, Athanassios; Patel, Jyoti D.; Johnson, David H.; Sandler, Alan; Villaflor, Victoria M.; Coon IV, John; Buckingham, Lela; Kaiser, Kelly; Basu, Sanjib; Bonomi, Philip.

In: Clinical Cancer Research, Vol. 14, No. 7, 01.04.2008, p. 2088-2094.

Research output: Contribution to journalArticle

Fidler, Mary Jo ; Argiris, Athanassios ; Patel, Jyoti D. ; Johnson, David H. ; Sandler, Alan ; Villaflor, Victoria M. ; Coon IV, John ; Buckingham, Lela ; Kaiser, Kelly ; Basu, Sanjib ; Bonomi, Philip. / The potential predictive value of cyclooxygenase-2 expression and increased risk of gastrointestinal hemorrhage in advanced non-small cell lung cancer patients treated with erlotinib and celecoxib. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 7. pp. 2088-2094.
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T1 - The potential predictive value of cyclooxygenase-2 expression and increased risk of gastrointestinal hemorrhage in advanced non-small cell lung cancer patients treated with erlotinib and celecoxib

AU - Fidler, Mary Jo

AU - Argiris, Athanassios

AU - Patel, Jyoti D.

AU - Johnson, David H.

AU - Sandler, Alan

AU - Villaflor, Victoria M.

AU - Coon IV, John

AU - Buckingham, Lela

AU - Kaiser, Kelly

AU - Basu, Sanjib

AU - Bonomi, Philip

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N2 - Purpose: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non - small cell lung cancer (NSCLC). With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC. Experimental Design: Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry. Results: Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21 patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P = 0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers. Conclusions: The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.

AB - Purpose: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non - small cell lung cancer (NSCLC). With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC. Experimental Design: Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry. Results: Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21 patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P = 0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers. Conclusions: The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.

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