Detection of EGFR Mutation in Malignant Pleural Effusion of Lung Cancer Patients and Cancer Cell Lines Establishment (EGFR)

Detection of Epithelial Growth Factor Receptor (EGFR) Mutation in Malignant Pleural Effusion of Lung Cancer Patients and Cancer Cell Lines Establishment

1. Detection EGFR mutation of cancer cells from malignant pleural effusion. 2. Established the cancer cell lines with without EGFR mutation from malignant pleural effusion.

Study Overview

• Status: Unknown
• Conditions: NSCLC
• Intervention / Treatment: Other: cancer cell lines establishment

Detailed Description

Lung cancer is the leading cause of mortality in the world. Previous study has shown that about 88% lung cancer cases belong to non-small cell lung cancer (NSCLC) in Taiwan (1). Approximately 50~90% of NSCLC patients had expression (or described as overexpression) of EGFR in cancer (2,3). Although targeting the EGFR kinase domain using the inhibitors gefitinib (Iressa) and erlotinib (Tarceva) has no effect against solid tumors, it achieves impressive response in subgroup of NSCLC especially in Asian ethnic background, female sex, the absence of a history of smoking, and a tumor with histologic feature of adenocarcinoma (3,4,5). Molecular studies of highly responsive cases revealed high percentage of somatic mutation within the tyrosine kinase, ATP-binding domain of the EGFR gene (6). One possible explanation for this phenomenon is that the cancer cells are "addicted" to signaling via the mutant EGFRs and die when the mutant oncoprotein is inactivated (7). However, specific mechanisms underlying epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) induced cell death have not been well delineated (7).

Approximately 90% of mutations affect a few specific amino acids. In-frame deletions in exon 19 centered on codons 756 to 750 make up 45~50% of mutations, and another 35~45% consist of the missense mutation leucine to arginine at codon 858 (L858R) in exon 21 (8, 9, 10). The link between EGFR-TKI response and EGFR mutations have been confirmed, but the increased prevalence of mutations in Asian (25%to 50%) compared with North American and Western European patients (10%) is currently unexplained (6,8-12). The response rate to TKI treatment in mutations-positive is 77% (30% to 100% with most series >60%) compared with 10% in mutation-negative cases (6). It is interesting that exon 19 deletion have increased response and survival with TKIs compared with L858R cases (10, 13, 14). This is in contrast to the natural history of patients, where those with exon 19 deletions appear to have shorter survival than those with L858R (8). The biological difference is still unknown and different mutations may have different biochemical signaling properties (15).

In this study, we will collect the pleural effusion from lung cancer patients. We will characterize the EGFR status of the cancer cell from malignant pleural effusion and try to establish the cancer cell lines from these patients. We hope to establish several cell lines with different mutations and then we can compare the difference responses and signal pathways in these cell lines. We can also explore the detailed mechanism of TKI responsive cancer cell and try to develop other agent to enhance the pathways.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chao-Chi Ho; Phone Number: +886-2-2356-2905; Email: ccho1203@ntu.edu.tw
    • Contact: Ming-Tzer Lin; Phone Number: +886-2-2356-2905; Email: lightpool@pchome.com.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All malignant pleural effusion related to NSCLC between April 2008 and March 2009.
• Older than 18 years old.
• The patients who received thoracentesis

Exclusion Criteria:

• The patients who are not compatible with inclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; We collected malignant pleural effusion for NSCLC cell lines with different EGFR mutations development and then we can compare the difference responses and signal pathways in these cell lines. We can also explore the detailed mechanism of TKI responsive cancer cell and try to develop other agent to enhance the pathways.	Other: cancer cell lines establishment; Detection of epithelial growth factor receptor (EGFR) mutation in malignant pleural effusion of lung cancer patients and cancer cell lines establishment; Other Names: EGFR mutation; NSCLC cell line establishment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
EGFR mutation in malignant pleural effusion of lung cancer patients cancer cell lines establishment	1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Chao-Chi Ho, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Anticipated): March 1, 2011
• Study Completion (Anticipated): March 1, 2011

Study Registration Dates

• First Submitted: September 10, 2008
• First Submitted That Met QC Criteria: September 12, 2008
• First Posted (Estimate): September 15, 2008

Study Record Updates

• Last Update Posted (Estimate): December 1, 2009
• Last Update Submitted That Met QC Criteria: November 25, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: EGFR mutation; Malignant pleural effusion; NSCLC cell line
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Pleural Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pleural Neoplasms; Pleural Effusion, Malignant; Pleural Effusion
• Other Study ID Numbers: 200804019R