PMID- 17974556
OWN - NLM
STAT- MEDLINE
DCOM- 20080416
LR  - 20220408
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 19
IP  - 4
DP  - 2008 Apr
TI  - EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory 
      colorectal cancer patients.
PG  - 717-23
AB  - BACKGROUND: Standardized conditions to distinguish subpopulations of colorectal 
      cancer (CRC) patients more and less sensitive to cetuximab therapy remain 
      undefined. MATERIALS AND METHODS: We retrospectively analyzed epidermal growth 
      factor receptor (EGFR) copy number by fluorescence in situ hybridization (FISH) 
      in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated 
      with cetuximab. Results were analyzed according to different score systems 
      previously reported in colorectal and lung cancers. The primary end point of the 
      study was identification of the EGFR FISH score that best associates with 
      response rate (RR). RESULTS: Using receiver operating characteristic (ROC) 
      analysis, the cut-off that best discriminated responders versus nonresponders to 
      cetuximab was a mean of 2.92 EGFR gene copies per cell. This model showed 
      sensitivity of 58.6% [95% confidence interval (CI) = 47.1-70.1) and specificity 
      of 93.3% (95% CI = 80.6-100). EGFR FISH-positive patients (N = 43, 50.6%) had 
      significantly higher RR (P = 0.0001) and significantly longer time to disease 
      progression (P = 0.02) than EGFR FISH negative (N = 42, 49.4%). Other scoring 
      systems resulted less accurate in discriminating patients with the highest 
      likelihood of response to cetuximab therapy. CONCLUSIONS: CRC patients with high 
      EGFR gene copy number have an increased likelihood to respond to cetuximab 
      therapy. Prospective clinical trials with a careful standardization of assay 
      conditions and pattern interpretation are urgently needed.
FAU - Cappuzzo, F
AU  - Cappuzzo F
AD  - Department of Medical Oncology, Istituto Clinico Humanitas IRCCS, Rozzano, Italy. 
      federico.cappuzzo@humanitas.it
FAU - Finocchiaro, G
AU  - Finocchiaro G
FAU - Rossi, E
AU  - Rossi E
FAU - Janne, P A
AU  - Janne PA
FAU - Carnaghi, C
AU  - Carnaghi C
FAU - Calandri, C
AU  - Calandri C
FAU - Bencardino, K
AU  - Bencardino K
FAU - Ligorio, C
AU  - Ligorio C
FAU - Ciardiello, F
AU  - Ciardiello F
FAU - Pressiani, T
AU  - Pressiani T
FAU - Destro, A
AU  - Destro A
FAU - Roncalli, M
AU  - Roncalli M
FAU - Crino, L
AU  - Crino L
FAU - Franklin, W A
AU  - Franklin WA
FAU - Santoro, A
AU  - Santoro A
FAU - Varella-Garcia, M
AU  - Varella-Garcia M
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20071031
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Cetuximab
MH  - Colorectal Neoplasms/*chemistry/*drug therapy/genetics/pathology
MH  - Confidence Intervals
MH  - Disease-Free Survival
MH  - *Drug Resistance, Neoplasm
MH  - ErbB Receptors/*analysis/genetics
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - *In Situ Hybridization, Fluorescence
MH  - Italy
MH  - Male
MH  - Middle Aged
MH  - Patient Selection
MH  - Predictive Value of Tests
MH  - ROC Curve
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Survival Analysis
MH  - Treatment Outcome
EDAT- 2007/11/03 09:00
MHDA- 2008/04/17 09:00
CRDT- 2007/11/03 09:00
PHST- 2007/11/03 09:00 [pubmed]
PHST- 2008/04/17 09:00 [medline]
PHST- 2007/11/03 09:00 [entrez]
AID - S0923-7534(19)41435-X [pii]
AID - 10.1093/annonc/mdm492 [doi]
PST - ppublish
SO  - Ann Oncol. 2008 Apr;19(4):717-23. doi: 10.1093/annonc/mdm492. Epub 2007 Oct 31.