First Line Gefitinib by FDG-PET Metabolic Response
Recruitment status was: Recruiting
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||First Line Gefitinib Treatment for Advanced Non-small Cell Lung Cancer (NSCLC) by the FDG-PET Metabolic Response|
- Objective Response rate [ Time Frame: one year ] [ Designated as safety issue: No ]The primary objective is to see the response rate of gefitinib in the patients who showed % decrease of peak SUV of main lesion 20% or more and continuously treated with gefitinib.
- Objective response rate by EGFR mutational status [ Time Frame: One year ] [ Designated as safety issue: No ]The secondary object is to see the relationship of changes in FDG uptake after gefitinib treatment with EGFR mutation; sensitivity, specificity, positive predictive value, and negative predictive value will be calculated comparing the groupings created by FDG-PET and actual EGFR mutational status.
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
After a baseline 18F FDG-PET, patients are treated with gefitinib 250mg/d as 1st line treatment for 7 days. And follow up 18F-FDG PET image is acquired after 1 week's treatment of gefitinib (with window period +/- 2 days).
If % decrease of peak SUV of main lesion is 20% or more, gefitinib treatment is continued till progression, unacceptable toxicities or patient's refusal. But if % decrease of peak SUV of main lesion less than 20% or peak SUV increase, gefitinib treatment is stopped, and changed to Pemetrexed/Cisplatin chemotherapy.
gefitinib 250mg/day daily
Other Name: Iressa
Gefitinib has anti-tumor activity as a result of EGFR tyrosine kinase inhibition, reducing multiple downstream signaling processes that activate cell proliferation and other cell responses, including cell migration angiogenesis, and reduced apoptosis. Recently, it has been approved for the first line treatment of advanced NSCLC that harbors EGFR mutation. In IPASS trial, tumors with EGFR mutation produced 71.2% of clinical response to first line gefitinib while tumors with wild type EGFR showed only 1.1% of response. Therefore, patient selection is critical for the clinical use of EGFR tyrosine kinase inhibitors as first line treatment.
When considering 1st line gefitinib treatment for NSCLC, we need EGFR mutational status of the tumor. But most patients do not give us such information at the time of diagnosis, because it requires tumor tissue and some time period for EGFR examination. So, we need other strategies such as using PET scan for early prediction of response to gefitinib.
Glucose metabolic activity closely reflects responses to gefitinib therapy. In preclinical study with gefitinib sensitive cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after treatment. And these metabolic alterations preceded changes in cell cycle distribution, thymidine uptake and apoptosis. In contrast, gefitinib resistant cells exhibited no measurable changes in FDG uptake, either in cell culture or in vivo.
The strategy using FDG-PET may guide us to perform 1st line geftinib. Recently investigators reported that FLT-PET or FDG-PET could predict response to EGFR tyrosine kinase (TKI) early after 1 week of treatment. And % decrease more than 20% of maximum SUV of main lesion after 1 week of EGFR TKI treatment could predict response to that drug. More than 20% decrease of SUV is a significant change during reproducibility test and also considered as a criteria for response prediction of paclitaxel/cisplatin chemotherapy.
So, investigators develop a protocol of 1st line gefitinib treatment for NSCLC according to FDG-PET response. And if the patient showed less than 20% decrease of peak SUV, investigators will stop gefitinib and treat him or her with the regimen of pemetrexed/cisplatin.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01510990
|Korea, Republic of|
|Asan Medical Center|
|Seoul, Korea, Republic of, 138-736|
|Principal Investigator:||Sang-We Kim, M.D.||Asan Medical Center|