title: Phase I/II trial of cilengitide with cetuximab, cisplatin and 5-fluorouracil in recurrent and/or metastatic squamous cell cancer of the head and neck: findings of the phase I part.
abstract: BACKGROUND
  Novel therapies are needed to improve the poor prognosis of patients with recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN).
  
  
  METHODS
  ADVANTAGE is a phase I/II, multicentre study evaluating the integrin inhibitor cilengitide combined with cetuximab and platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN. The phase I part tested cilengitide (500, 1000 and 2000 mg) twice weekly with standard doses of cetuximab, cisplatin and 5-fluorouracil.
  
  
  RESULTS
  Ten patients (9 male, 1 female; median 56 years old) were included in the phase I part. No dose-limiting toxicities (DLTs: grade 3/4 toxicities in the first 3 weeks as defined per protocol) or deaths occurred. The most common adverse events (AEs) were constipation, rash, nausea, anorexia and fatigue. Cilengitide-related grade 3/4 AEs, all of which occurred after the DLT observation period, were anaemia, angioedema, asthenia, mucosal inflammation, nausea and vomiting (one event per category). Best overall tumour response was partial response (PR) for 4 out of 10 patients and stable disease (SD) for 6 out of 10 patients across all cohorts. Disease control rate (complete response, PR and SD) was 100%.
  
  
  CONCLUSIONS
  Cilengitide combined with cetuximab and platinum-based chemotherapy was well tolerated. No DLTs or unexpected AEs were observed. Cilengitide 2000 mg was considered safe and was selected for the subsequent randomised phase II part assessing progression-free survival.
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium. Jan.B.Vermorken@uza.be
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: J
authors.initials: J
authors.lastname: Guigay
authors.forename: R
authors.initials: R
authors.lastname: Mesia
authors.forename: J M
authors.initials: JM
authors.lastname: Trigo
authors.forename: U
authors.initials: U
authors.lastname: Keilholz
authors.forename: A
authors.initials: A
authors.lastname: Kerber
authors.forename: U
authors.initials: U
authors.lastname: Bethe
authors.forename: M
authors.initials: M
authors.lastname: Picard
authors.forename: T H
authors.initials: TH
authors.lastname: Brummendorf
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil