PMID- 19276157
OWN - NLM
STAT- MEDLINE
DCOM- 20090608
LR  - 20200930
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 8
IP  - 3
DP  - 2009 Mar
TI  - Molecular determinants of response to matuzumab in combination with paclitaxel 
      for patients with advanced non-small cell lung cancer.
PG  - 481-9
LID - 10.1158/1535-7163.MCT-08-1068 [doi]
AB  - Antibodies targeting epidermal growth factor receptor (EGFR) have proven to be 
      effective in patients with non-small cell lung cancer (NSCLC) that express EGFR. 
      We recently published a phase I study of weekly matuzumab plus paclitaxel. This 
      therapy was well tolerated and showed clinical responses in the majority of 
      patients. Although matuzumab displays potent antitumor activity in some patients, 
      not all patients respond well to treatment. Whether dysregulation of 
      EGFR-mediated pathways precludes or sensitizes cells to paclitaxel is unknown. We 
      sought to determine molecular predictive factors for therapy response in a phase 
      I/II study patient cohort treated with matuzumab+/-paclitaxel. Twenty-three cases 
      [including one complete response (CR), three partial responses (PR), 10 stable 
      diseases (SD)] were screened using immunohistochemistry (IHC), fluorescence in 
      situ hybridization (FISH), PCR/sequencing and denaturing wave high performance 
      liquid chromatography (D-HPLC) for expression, amplification, and mutation status 
      of EGFR and downstream signaling pathways. All patients with PR or CR displayed 
      an either high overall or single-cell EGFR expression in the majority of cells. 
      In addition, all of the moderate responders, who achieved SD after at least two 
      cycles of therapy, showed diffuse EGFR expression rates and/or strong single-cell 
      EGFR expression. In contrast, 44% of the nonresponders showed low overall or 
      single-cell EGFR expression levels. No low-expressing EGFR cases were present 
      within the responder group. In addition, among patients with a gain-of-function 
      mutation in KRAS primary therapy failure and/or short responses to therapy were 
      observed. Our data suggest that EGFR expression and KRAS mutation status is 
      predictive for clinical response to matuzumab +/- paclitaxel in patients with 
      advanced NSCLC.
FAU - Schittenhelm, Marcus M
AU  - Schittenhelm MM
AD  - University Hospital Tubingen, Department of Hematology, Oncology, Rheumatology, 
      Immunology and Pulmonology, Otfried-Muller-Strasse 10, 72074 Tubingen, Germany. 
      marcus.schittenhelm@med.uni-tuebingen.de
FAU - Kollmannsberger, Christian
AU  - Kollmannsberger C
FAU - Oechsle, Karin
AU  - Oechsle K
FAU - Harlow, Amy
AU  - Harlow A
FAU - Morich, Jason
AU  - Morich J
FAU - Honecker, Friedemann
AU  - Honecker F
FAU - Kurek, Raffael
AU  - Kurek R
FAU - Storkel, Stephan
AU  - Storkel S
FAU - Kanz, Lothar
AU  - Kanz L
FAU - Corless, Christopher L
AU  - Corless CL
FAU - Wong, Kwok-Kin
AU  - Wong KK
FAU - Bokemeyer, Carsten
AU  - Bokemeyer C
FAU - Heinrich, Michael C
AU  - Heinrich MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090310
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - MG4M3QB242 (matuzumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/*drug therapy/genetics/pathology
MH  - Clinical Trials, Phase I as Topic
MH  - Clinical Trials, Phase II as Topic
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, erbB-1
MH  - Humans
MH  - Lung Neoplasms/diagnosis/*drug therapy/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/*administration & dosage
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Retrospective Studies
MH  - ras Proteins/genetics
EDAT- 2009/03/12 09:00
MHDA- 2009/06/09 09:00
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/06/09 09:00 [medline]
AID - 1535-7163.MCT-08-1068 [pii]
AID - 10.1158/1535-7163.MCT-08-1068 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2009 Mar;8(3):481-9. doi: 10.1158/1535-7163.MCT-08-1068. Epub 
      2009 Mar 10.