PMID- 28872582
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 9
IP  - 9
DP  - 2017 Sep 5
TI  - Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a 
      Marker for Improved Survival of Head and Neck Cancer Patients.
LID - 10.3390/cancers9090117 [doi]
LID - 117
AB  - Targeting of alpha(V)beta3 and alpha(V)beta5 integrins by cilengitide may reduce growth of 
      solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical 
      investigations suggest increased activity of cilengitide in combination with 
      other treatment modalities. The only published trial in HNSCC (ADVANTAGE) 
      investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once 
      (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic 
      HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower 
      adverse events (AEs) compared to PFE but not the benefit in overall survival 
      expected based on preclinical data. As we found in the FLAVINO assay, a 
      short-time ex vivo assay for prediction of chemosensitivity, only a subgroup of 
      HNSCC had an increased suppressive effect of cilengitide containing combination 
      therapies on colony formation of epithelial cells (CF(ec)) and release of 
      pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to 
      respond. Response to alpha(V)beta3 and alpha(V)beta5 integrin targeting by cilengitide 
      classifies HNSCC regarding outcome. We present FLAVINO data arguing for further 
      development of cilengitide plus cetuximab in treatment of a subgroup of HNSCC 
      potentially identified by the FLAVINO assay using a set of biomarkers for 
      response evaluation.
FAU - Cedra, Susan
AU  - Cedra S
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 
      Leipzig, Germany. scedra@gmx.net.
FAU - Wiegand, Susanne
AU  - Wiegand S
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 
      Leipzig, Germany. Susanne.Wiegand@medizin.uni-leipzig.de.
FAU - Kolb, Marlen
AU  - Kolb M
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 
      Leipzig, Germany. Marlen.Kolb@medizin.uni-leipzig.de.
FAU - Dietz, Andreas
AU  - Dietz A
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 
      Leipzig, Germany. andreas.dietz@medizin.uni-leipzig.de.
FAU - Wichmann, Gunnar
AU  - Wichmann G
AD  - Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 
      Leipzig, Germany. gunnar.wichmann@medizin.uni-leipzig.de.
LA  - eng
PT  - Journal Article
DEP - 20170905
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC5615332
OTO - NOTNLM
OT  - biomarker
OT  - chemoresponse ex vivo
OT  - cilengitide
OT  - head and neck cancer
OT  - head and neck squamous cell carcinoma (HNSCC)
OT  - integrin
OT  - interleukin 6
OT  - monocyte chemotactic protein-1
OT  - predictive assay
OT  - targeted therapy
OT  - alphaVbeta3
COIS- GW received funding for the project "Cilengitide in HNSCC ex vivo" and honoraria 
      and travel expenses from Merck Serono GmbH. The other authors all declare no 
      conflict of interest. The founding sponsor Merck has no role in the design of the 
      study; in the collection, analyses, or interpretation of data; in the writing of 
      the manuscript, or in the decision to publish the results.
EDAT- 2017/09/06 06:00
MHDA- 2017/09/06 06:01
PMCR- 2017/09/05
CRDT- 2017/09/06 06:00
PHST- 2017/06/30 00:00 [received]
PHST- 2017/08/18 00:00 [revised]
PHST- 2017/09/02 00:00 [accepted]
PHST- 2017/09/06 06:00 [entrez]
PHST- 2017/09/06 06:00 [pubmed]
PHST- 2017/09/06 06:01 [medline]
PHST- 2017/09/05 00:00 [pmc-release]
AID - cancers9090117 [pii]
AID - cancers-09-00117 [pii]
AID - 10.3390/cancers9090117 [doi]
PST - epublish
SO  - Cancers (Basel). 2017 Sep 5;9(9):117. doi: 10.3390/cancers9090117.