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Cancers 2017, 9(9), 117; https://doi.org/10.3390/cancers9090117

Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients

Department of Otolaryngology, Head and Neck Surgery, University of Leipzig, 04103 Leipzig, Germany
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Academic Editor: Helen M. Sheldrake
Received: 30 June 2017 / Revised: 18 August 2017 / Accepted: 2 September 2017 / Published: 5 September 2017
(This article belongs to the Special Issue Integrins in Cancer)
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Abstract

Targeting of αVβ3 and αVβ5 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 (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to respond. Response to αVβ3 and αVβ5 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. View Full-Text
Keywords: head and neck cancer; head and neck squamous cell carcinoma (HNSCC); predictive assay; chemoresponse ex vivo; cilengitide; integrin; αVβ3; targeted therapy; biomarker; interleukin 6; monocyte chemotactic protein-1 head and neck cancer; head and neck squamous cell carcinoma (HNSCC); predictive assay; chemoresponse ex vivo; cilengitide; integrin; αVβ3; targeted therapy; biomarker; interleukin 6; monocyte chemotactic protein-1
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Cedra, S.; Wiegand, S.; Kolb, M.; Dietz, A.; Wichmann, G. Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients. Cancers 2017, 9, 117.

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