title: Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part).
abstract: BACKGROUND
  Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy.
  
  
  METHODS
  The phase I/II study ADVANTAGE evaluated cilengitide combined with cisplatin, 5-fluorouracil, and cetuximab (PFE) in R/M-SCCHN. The phase II part reported here was an open-label, randomized, controlled trial investigating progression-free survival (PFS). Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFE-alone arm: cetuximab only) until disease progression or unacceptable toxicity.
  
  
  RESULTS
  One hundred and eighty-two patients were treated. Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). Accordingly, median overall survival and objective response rates were not improved with cilengitide (12.4 months/47%, 10.6 months/27%, and 11.6 months/36%, respectively). No clinically meaningful safety differences were observed between groups. None of the tested biomarkers (expression of integrins, CD31, Ki-67, vascular endothelial growth factor receptor 2, vascular endothelial-cadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus) were predictive of outcome.
  
  
  CONCLUSIONS
  Neither of the cilengitide-containing regimens demonstrated a PFS benefit over PFE alone in R/M-SCCHN patients.
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium. Electronic address: jan.b.vermorken@uza.be.
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.affiliation: Medical Oncology Service, Center Antoine Lacassagne, Nice, France.
authors.forename: F
authors.initials: F
authors.lastname: Peyrade
authors.affiliation: Medical Oncology, National Center for Tumor Diseases (NCT), Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krauss
authors.affiliation: Medical Oncology Service, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Mesía
authors.affiliation: Head and Neck Surgery, National Oncology Institute, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Remenar
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen.
authors.forename: T C
authors.initials: TC
authors.lastname: Gauler
authors.affiliation: Department of Hematology and Medical Oncology, Charité Campus Benjamin Franklin, Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.affiliation: Clinical Research Unit, Institute Claudius Regaud, Toulouse, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Delord
authors.affiliation: II Medical Clinic and Polyclinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Schafhausen
authors.affiliation: Onco-radiology, Jósa András Teaching Hospital, Nyíregyháza, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Erfán
authors.affiliation: Department of Hematology and Oncology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: T H
authors.initials: TH
authors.lastname: Brümmendorf
authors.affiliation: Lung and Head and Neck Cancer Unit, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Iglesias
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bethe
authors.affiliation: Merck KGaA, Darmstadt, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hicking
authors.affiliation: Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: P M
authors.initials: PM
authors.lastname: Clement
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D000068818:Cetuximab; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012910:Snake Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012910:Snake Venoms; C422910:Cilengitide; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil
keywords: cetuximab; cilengitide; integrin inhibitor; phase I/II; platinum-based chemotherapy with 5-fluorouracil; recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN)