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A Phase II Study of Gefitinib Monotherapy in Advanced Esophageal Adenocarcinoma: Evidence of Gene Expression, Cellular, and Clinical Response

A Phase II Study of Gefitinib Monotherapy in Advanced Esophageal Adenocarcinoma: Evidence of Gene... Purpose: At presentation, most cases of adenocarcinoma of the esophagus (ACE) are inoperable. Although chemotherapy can prolong survival, patients eventually die as a result of refractory disease. Epidermal growth factor receptor (EGFR) is almost universally expressed in ACE and is a negative prognostic factor. Experimental Design: This open-label, two-center, noncomparative, two-part phase II trial assessed the EGFR tyrosine kinase inhibitor gefitinib (500 mg/d) in patients with advanced, inoperable ACE. The primary end point was tumor response. The effect of EGFR inhibition was also evaluated by gene expression analysis of tumor biopsies taken before gefitinib treatment and 28 days after. Results: Twenty-seven patients were recruited and evaluable for tumor response and safety. Three patients had a partial response and seven had stable disease, giving a disease control rate (partial response + stable disease) of 37%. Drug-related adverse events were generally mild: diarrhea in 19 (grade 3 in three) and rash in 19 (grade 3 in five) patients, and there were no grade 4 drug-related adverse events. Microarray experiments on tumor biopsies showed that gefitinib also down-regulated oncogenes associated with tumor progression. Ki67 (a marker of tumor growth) expression decreased in five of seven biopsies taken before and after treatment. Conclusion: Gefitinib (500 mg/d) is an active and generally well-tolerated treatment for ACE. Studies on endoscopic biopsies are feasible and indicate that gefitinib inhibits both gene expression and cellular biology at 500 mg/d, and these may provide surrogate end points for predictive biomarkers. Further trials of gefitinib are warranted, particularly as patient response seems to be durable and current second-line chemotherapy options have no proven ability to prolong life. esophageal cancer clinical trial http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Cancer Research American Association of Cancer Research

A Phase II Study of Gefitinib Monotherapy in Advanced Esophageal Adenocarcinoma: Evidence of Gene Expression, Cellular, and Clinical Response

A Phase II Study of Gefitinib Monotherapy in Advanced Esophageal Adenocarcinoma: Evidence of Gene Expression, Cellular, and Clinical Response

Clinical Cancer Research , Volume 13 (19): 5869 – Oct 1, 2007

Abstract

Purpose: At presentation, most cases of adenocarcinoma of the esophagus (ACE) are inoperable. Although chemotherapy can prolong survival, patients eventually die as a result of refractory disease. Epidermal growth factor receptor (EGFR) is almost universally expressed in ACE and is a negative prognostic factor. Experimental Design: This open-label, two-center, noncomparative, two-part phase II trial assessed the EGFR tyrosine kinase inhibitor gefitinib (500 mg/d) in patients with advanced, inoperable ACE. The primary end point was tumor response. The effect of EGFR inhibition was also evaluated by gene expression analysis of tumor biopsies taken before gefitinib treatment and 28 days after. Results: Twenty-seven patients were recruited and evaluable for tumor response and safety. Three patients had a partial response and seven had stable disease, giving a disease control rate (partial response + stable disease) of 37%. Drug-related adverse events were generally mild: diarrhea in 19 (grade 3 in three) and rash in 19 (grade 3 in five) patients, and there were no grade 4 drug-related adverse events. Microarray experiments on tumor biopsies showed that gefitinib also down-regulated oncogenes associated with tumor progression. Ki67 (a marker of tumor growth) expression decreased in five of seven biopsies taken before and after treatment. Conclusion: Gefitinib (500 mg/d) is an active and generally well-tolerated treatment for ACE. Studies on endoscopic biopsies are feasible and indicate that gefitinib inhibits both gene expression and cellular biology at 500 mg/d, and these may provide surrogate end points for predictive biomarkers. Further trials of gefitinib are warranted, particularly as patient response seems to be durable and current second-line chemotherapy options have no proven ability to prolong life. esophageal cancer clinical trial

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Publisher
American Association of Cancer Research
Copyright
Copyright © 2010 American Association for Cancer Research
ISSN
1078-0432
eISSN
1557-3265
DOI
10.1158/1078-0432.CCR-06-1970
pmid
17908981
Publisher site
See Article on Publisher Site

Abstract

Purpose: At presentation, most cases of adenocarcinoma of the esophagus (ACE) are inoperable. Although chemotherapy can prolong survival, patients eventually die as a result of refractory disease. Epidermal growth factor receptor (EGFR) is almost universally expressed in ACE and is a negative prognostic factor. Experimental Design: This open-label, two-center, noncomparative, two-part phase II trial assessed the EGFR tyrosine kinase inhibitor gefitinib (500 mg/d) in patients with advanced, inoperable ACE. The primary end point was tumor response. The effect of EGFR inhibition was also evaluated by gene expression analysis of tumor biopsies taken before gefitinib treatment and 28 days after. Results: Twenty-seven patients were recruited and evaluable for tumor response and safety. Three patients had a partial response and seven had stable disease, giving a disease control rate (partial response + stable disease) of 37%. Drug-related adverse events were generally mild: diarrhea in 19 (grade 3 in three) and rash in 19 (grade 3 in five) patients, and there were no grade 4 drug-related adverse events. Microarray experiments on tumor biopsies showed that gefitinib also down-regulated oncogenes associated with tumor progression. Ki67 (a marker of tumor growth) expression decreased in five of seven biopsies taken before and after treatment. Conclusion: Gefitinib (500 mg/d) is an active and generally well-tolerated treatment for ACE. Studies on endoscopic biopsies are feasible and indicate that gefitinib inhibits both gene expression and cellular biology at 500 mg/d, and these may provide surrogate end points for predictive biomarkers. Further trials of gefitinib are warranted, particularly as patient response seems to be durable and current second-line chemotherapy options have no proven ability to prolong life. esophageal cancer clinical trial

Journal

Clinical Cancer ResearchAmerican Association of Cancer Research

Published: Oct 1, 2007

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