PMID- 21653686
OWN - NLM
STAT- MEDLINE
DCOM- 20111123
LR  - 20220409
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 15
DP  - 2011 Aug 1
TI  - Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous 
      cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment.
PG  - 5197-204
LID - 10.1158/1078-0432.CCR-10-3338 [doi]
AB  - PURPOSE: Constitutive activation of epidermal growth factor receptor (EGFR) as a 
      result of gene amplification, mutation, or overexpression of its ligands has been 
      associated with response to EGFR targeting strategies. The role of these 
      molecular mechanisms for the responsiveness of squamous cell carcinoma of the 
      head and neck (SCCHN) to cetuximab-containing regimens remains unknown. 
      EXPERIMENTAL DESIGN: Tumor biopsies from 47 patients, enrolled in a single-arm 
      phase II multicenter study for second-line treatment of recurrent or metastatic 
      SCCHN with cetuximab and docetaxel, were analyzed by immunohistochemistry for 
      expression of EGFR, its deletion variant III (EGFRvIII) and its ligand 
      amphiregulin (AREG). The relation between expression levels and disease control 
      rate (DCR) was evaluated by logistic regression. Association between expression 
      levels, progression-free survival (PFS), and overall survival (OS) was determined 
      by Kaplan-Meier analysis, log-rank test, and uni- and multivariate Cox regression 
      analysis. RESULTS: High expression of EGFR, EGFRvIII, and AREG was detected in 
      73%, 17%, and 45% of SCCHN cases, respectively. Expression levels of EGFR had no 
      impact on PFS or OS. High expression levels of EGFRvIII were significantly 
      associated with reduced DCR and shortened PFS (HR: 3.3, P = 0.005) but not with 
      OS. Patients with high AREG expression in tumor cells had significantly shortened 
      OS (HR: 2.2, P = 0.002) and PFS (HR 2.2, P = 0.019) compared with patients with 
      low expression score. Multivariate Cox analysis revealed an independent 
      association of AREG and EGFRvIII with PFS but only AREG was an independent 
      prognosticator of OS. CONCLUSIONS: High EGFRvIII and AREG expression levels 
      identify SCCHN patients who are less likely to benefit from combination treatment 
      with cetuximab and docetaxel.
CI  - (c)2011 AACR.
FAU - Tinhofer, Ingeborg
AU  - Tinhofer I
AD  - Department of Radiotherapy Campus Mitte, Translational Radiobiology and 
      Radiooncology Research Laboratory, Charite Universiteuroatsmedizin Berlin, 
      Chariteplatz 1, 10117Berlin, Germany. ingeborg.tinhofer@charite.de
FAU - Klinghammer, Konrad
AU  - Klinghammer K
FAU - Weichert, Wilko
AU  - Weichert W
FAU - Knodler, Maren
AU  - Knodler M
FAU - Stenzinger, Albrecht
AU  - Stenzinger A
FAU - Gauler, Thomas
AU  - Gauler T
FAU - Budach, Volker
AU  - Budach V
FAU - Keilholz, Ulrich
AU  - Keilholz U
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110608
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Taxoids)
RN  - 0 (epidermal growth factor receptor VIII)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - PQX0D8J21J (Cetuximab)
SB  - IM
MH  - Amphiregulin
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma, Squamous Cell/*drug therapy/*metabolism
MH  - Cetuximab
MH  - Docetaxel
MH  - EGF Family of Proteins
MH  - ErbB Receptors/*metabolism
MH  - Glycoproteins/*metabolism
MH  - Head and Neck Neoplasms/*drug therapy/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Squamous Cell Carcinoma of Head and Neck
MH  - Taxoids/*administration & dosage
MH  - Treatment Outcome
EDAT- 2011/06/10 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/06/10 06:00
PHST- 2011/06/10 06:00 [entrez]
PHST- 2011/06/10 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 1078-0432.CCR-10-3338 [pii]
AID - 10.1158/1078-0432.CCR-10-3338 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Aug 1;17(15):5197-204. doi: 10.1158/1078-0432.CCR-10-3338. 
      Epub 2011 Jun 8.