PMID- 17538169
OWN - NLM
STAT- MEDLINE
DCOM- 20070612
LR  - 20181201
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 25
IP  - 16
DP  - 2007 Jun 1
TI  - Prospective study of gefitinib in epidermal growth factor receptor fluorescence 
      in situ hybridization-positive/phospho-Akt-positive or never smoker patients with 
      advanced non-small-cell lung cancer: the ONCOBELL trial.
PG  - 2248-55
AB  - PURPOSE: In non-small-cell lung cancer (NSCLC), clinical and biologic predictors 
      for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity 
      have been identified in retrospective studies, and there is urgent need to 
      validate these results in prospective trials. The ONCOBELL trial is a prospective 
      phase II study evaluating gefitinib sensitivity in NSCLC patients who never 
      smoked or have increased EGFR gene copy number or activation of the antiapoptotic 
      protein Akt. PATIENTS AND METHODS: EGFR gene copy number was evaluated using 
      fluorescence in situ hybridization (FISH), and presence of phospho-Akt was 
      evaluated using immunohistochemistry. Additional tests included 
      immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation 
      analysis of EGFR, HER2, and K-ras. RESULTS: From November 2004 to February 2006, 
      183 patients were screened, and 42 patients were enrolled onto the trial. We 
      observed one complete and 19 partial responses, for an overall response rate (RR) 
      of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months, 
      median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, 
      and median survival time was not reached. EGFR FISH-positive patients, compared 
      with negative patients, had higher RR (68.0% v 9.1%, respectively; P < .001), 
      longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer 
      survival (median survival not reached v 7.4 months, respectively; P = .3). 
      Therapy was well tolerated, and there were no drug-related deaths. Median 
      follow-up time was too short for significance tests of differences in survival 
      outcomes. CONCLUSION: Gefitinib is active and well tolerated in patients with 
      trial characteristics, and EGFR FISH analysis is an accurate predictor for such 
      therapy.
FAU - Cappuzzo, Federico
AU  - Cappuzzo F
AD  - Department of Hematology-Oncology, Istituto Clinico Humanitas IRCCS, Rozzano, 
      Italy. federico.cappuzzo@humanitas.it
FAU - Ligorio, Claudia
AU  - Ligorio C
FAU - Janne, Pasi A
AU  - Janne PA
FAU - Toschi, Luca
AU  - Toschi L
FAU - Rossi, Elisa
AU  - Rossi E
FAU - Trisolini, Rocco
AU  - Trisolini R
FAU - Paioli, Daniela
AU  - Paioli D
FAU - Holmes, Alison J
AU  - Holmes AJ
FAU - Magrini, Elisabetta
AU  - Magrini E
FAU - Finocchiaro, Giovanna
AU  - Finocchiaro G
FAU - Bartolini, Stefania
AU  - Bartolini S
FAU - Cancellieri, Alessandra
AU  - Cancellieri A
FAU - Ciardiello, Fortunato
AU  - Ciardiello F
FAU - Patelli, Marco
AU  - Patelli M
FAU - Crino, Lucio
AU  - Crino L
FAU - Varella-Garcia, Marileila
AU  - Varella-Garcia M
LA  - eng
GR  - 1K12CA87723-01/CA/NCI NIH HHS/United States
GR  - 1R01CA114465-01/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinazolines)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - Nat Clin Pract Oncol. 2008 Jan;5(1):10-1. PMID: 17955045
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/chemistry/*drug therapy/mortality
MH  - ErbB Receptors/*analysis/genetics
MH  - Female
MH  - Gefitinib
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/chemistry/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Phosphorylation
MH  - Prospective Studies
MH  - Proto-Oncogene Proteins c-akt/*analysis
MH  - Quinazolines/adverse effects/*therapeutic use
MH  - Smoking
EDAT- 2007/06/01 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/06/01 09:00
PHST- 2007/06/01 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/06/01 09:00 [entrez]
AID - 25/16/2248 [pii]
AID - 10.1200/JCO.2006.09.4300 [doi]
PST - ppublish
SO  - J Clin Oncol. 2007 Jun 1;25(16):2248-55. doi: 10.1200/JCO.2006.09.4300.