A Phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer

Robert Mutter, Bo Lu, David P.Carbone, Ildiko Csiki, Luigi Moretti, David H. Johnson, Jason D. Morrow, Alan B. Sandler, Yu Shyr, Fei Ye, Hak Choy

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Purpose: Cyclooxygenase (COX) -2 up-regulation plays an important role in the pathogenesis of lung cancer. Selective COX-2 inhibitors have promoted chemosensitivity and radiosensitivity of tumor cells in preclinical trials. Experimental Design: In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition. Results: Seventeen patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled in the study. All received 400 mg celecoxib twice daily continuously while on trial in addition to concurrent chemoradiation therapy with paclitaxel and carboplatin. Celecoxib was continued until disease progression. The overall objective response rate was 42.9%, and the median overall survival time was 203 days. In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E 2, after 1 week of celecoxib administration. Patients with very high levels of PGE-M before initiation of therapy also responded poorly to therapy. Serum vascular endothelial growth factor levels did not predict response or survival. Conclusion: The trial was terminated because it did not meet the predetermined goal of 80% overall response rate. In unselected patients, the addition of celecoxib to concurrent chemoradiotherapy with inoperable stage IIIA/B NSCLC does not improve survival. Urinary PGE-M is a promising biomarker for predicting response to COX-2 inhibition in NSCLC.

Original languageEnglish (US)
Pages (from-to)2158-2165
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - Mar 15 2009

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Celecoxib
Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Radiotherapy
Cyclooxygenase 2
Survival
Biomarkers
Cyclooxygenase 2 Inhibitors
Radiation Tolerance
Chemoradiotherapy
Prostaglandins E
Vascular Endothelial Growth Factor A
Disease Progression
Lung Neoplasms
Research Design
Up-Regulation
Therapeutics
Acids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A Phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer. / Mutter, Robert; Lu, Bo; P.Carbone, David; Csiki, Ildiko; Moretti, Luigi; Johnson, David H.; Morrow, Jason D.; Sandler, Alan B.; Shyr, Yu; Ye, Fei; Choy, Hak.

In: Clinical Cancer Research, Vol. 15, No. 6, 15.03.2009, p. 2158-2165.

Research output: Contribution to journalArticle

Mutter, Robert ; Lu, Bo ; P.Carbone, David ; Csiki, Ildiko ; Moretti, Luigi ; Johnson, David H. ; Morrow, Jason D. ; Sandler, Alan B. ; Shyr, Yu ; Ye, Fei ; Choy, Hak. / A Phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 6. pp. 2158-2165.
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abstract = "Purpose: Cyclooxygenase (COX) -2 up-regulation plays an important role in the pathogenesis of lung cancer. Selective COX-2 inhibitors have promoted chemosensitivity and radiosensitivity of tumor cells in preclinical trials. Experimental Design: In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition. Results: Seventeen patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled in the study. All received 400 mg celecoxib twice daily continuously while on trial in addition to concurrent chemoradiation therapy with paclitaxel and carboplatin. Celecoxib was continued until disease progression. The overall objective response rate was 42.9{\%}, and the median overall survival time was 203 days. In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E 2, after 1 week of celecoxib administration. Patients with very high levels of PGE-M before initiation of therapy also responded poorly to therapy. Serum vascular endothelial growth factor levels did not predict response or survival. Conclusion: The trial was terminated because it did not meet the predetermined goal of 80{\%} overall response rate. In unselected patients, the addition of celecoxib to concurrent chemoradiotherapy with inoperable stage IIIA/B NSCLC does not improve survival. Urinary PGE-M is a promising biomarker for predicting response to COX-2 inhibition in NSCLC.",
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T1 - A Phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer

AU - Mutter, Robert

AU - Lu, Bo

AU - P.Carbone, David

AU - Csiki, Ildiko

AU - Moretti, Luigi

AU - Johnson, David H.

AU - Morrow, Jason D.

AU - Sandler, Alan B.

AU - Shyr, Yu

AU - Ye, Fei

AU - Choy, Hak

PY - 2009/3/15

Y1 - 2009/3/15

N2 - Purpose: Cyclooxygenase (COX) -2 up-regulation plays an important role in the pathogenesis of lung cancer. Selective COX-2 inhibitors have promoted chemosensitivity and radiosensitivity of tumor cells in preclinical trials. Experimental Design: In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition. Results: Seventeen patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled in the study. All received 400 mg celecoxib twice daily continuously while on trial in addition to concurrent chemoradiation therapy with paclitaxel and carboplatin. Celecoxib was continued until disease progression. The overall objective response rate was 42.9%, and the median overall survival time was 203 days. In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E 2, after 1 week of celecoxib administration. Patients with very high levels of PGE-M before initiation of therapy also responded poorly to therapy. Serum vascular endothelial growth factor levels did not predict response or survival. Conclusion: The trial was terminated because it did not meet the predetermined goal of 80% overall response rate. In unselected patients, the addition of celecoxib to concurrent chemoradiotherapy with inoperable stage IIIA/B NSCLC does not improve survival. Urinary PGE-M is a promising biomarker for predicting response to COX-2 inhibition in NSCLC.

AB - Purpose: Cyclooxygenase (COX) -2 up-regulation plays an important role in the pathogenesis of lung cancer. Selective COX-2 inhibitors have promoted chemosensitivity and radiosensitivity of tumor cells in preclinical trials. Experimental Design: In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition. Results: Seventeen patients with stage IIIA or IIIB non-small cell lung cancer (NSCLC) were enrolled in the study. All received 400 mg celecoxib twice daily continuously while on trial in addition to concurrent chemoradiation therapy with paclitaxel and carboplatin. Celecoxib was continued until disease progression. The overall objective response rate was 42.9%, and the median overall survival time was 203 days. In contrast to nonresponders, those patients with complete and partial responses had a significant decrease in the level of urinary 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), the major metabolite of prostaglandin E 2, after 1 week of celecoxib administration. Patients with very high levels of PGE-M before initiation of therapy also responded poorly to therapy. Serum vascular endothelial growth factor levels did not predict response or survival. Conclusion: The trial was terminated because it did not meet the predetermined goal of 80% overall response rate. In unselected patients, the addition of celecoxib to concurrent chemoradiotherapy with inoperable stage IIIA/B NSCLC does not improve survival. Urinary PGE-M is a promising biomarker for predicting response to COX-2 inhibition in NSCLC.

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