2006 Fiscal Year Final Research Report Summary
Analysis of EGFR inhibitor and/or COX-2 inhibitor sensitivity for clinical application in lung cancer.
| Project/Area Number |
17590811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
HIDA Toyoaki Aichi Cancer Center Research Institute, Molecular Oncology, Researcher, 分子腫瘍学部, 研究員 (80250249)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Lung cancer / Molecular targeted therapy / COX2 inhibitor / EGFR inhibitor / Growth suppression / Combination / Gene mutation / Clinical trial |
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| Research Abstract |
We performed mutational analyses of exon 19 deletion and the L858R point mutation of the EGFR gene. Exon 19 deletion was determined by common fragment analysis, and L858R mutation was detected by the cycleave real-time quantitative PCR technique. Using this method, we evaluated the efficacy of gefitinib monotherapy prospectively in patients with advanced or pretreated non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Mutations of the EGFR gene were detected in 27 (41%) of 66 patients. Ten had exon 19 deletion and 17 had L858R. Twenty-one patients harboring EGFR mutations were treated with gefitinib and were considered assessable for responses and adverse events. Nineteen patients with EGFR mutations achieved objective responses (three complete responses and 16 partial responses) resulting in an overall response rate of 90.5% (95% confidence interval (CI), 69.6%-98.8%). The median progression-free survival was 7.7 months (95% CI, 6.0 months to not reached). We also studied 14 tumors with acquired resistance to gefitinib for secondary mutations occurring in the EGFR tyrosine kinase domain. Seven of the 14 tumors had a secondary T790M mutation. Because our present study also indicated the cooperative inhibitory effect by simultaneously blocking EGFR-and COX-2-mediated pathways, combination of EGFR inhibitor and COX-2 inhibitor may provide a promising strategy for lung cancer therapy.
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