title: Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.
  
  
  RESULTS
  Fifty-three patients were enrolled onto the study. The incidence of dose-limiting toxicities in phase A was acceptable. The most common grade 3/4 adverse events in both groups were leucopenia (38%), asthenia (25%), vomiting (14%), and thrombocytopenia (15%), which are consistent with the known safety profiles of cetuximab, cisplatin/carboplatin, and FU. The overall response rate among patients was 36%, with no clear trend toward an increased efficacy at the highest dose of FU, and no impact of the concomitant chemotherapy regimens on cetuximab pharmacokinetics.
  
  
  CONCLUSIONS
  The combination of cetuximab, cisplatin/carboplatin, and FU was reasonably well tolerated and active in recurrent/metastatic SCCHN, and merits additional investigation. An FU dose of 1,000 mg/m2/d in combination with cisplatin or carboplatin can be recommended for additional studies.
authors.affiliation: Institut Gustave Roussy, Radiothérapie, Villejuif, France. bourhis@igr.fr
authors.forename: Jean
authors.initials: J
authors.lastname: Bourhis
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesia
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.forename: Lionel
authors.initials: L
authors.lastname: Geoffrois
authors.forename: Christian
authors.initials: C
authors.lastname: Borel
authors.forename: Yves
authors.initials: Y
authors.lastname: Humblet
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Pousa
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hitt
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Vega Villegas
authors.forename: Lionel
authors.initials: L
authors.lastname: Duck
authors.forename: Dominique
authors.initials: D
authors.lastname: Rosine
authors.forename: Nadia
authors.initials: N
authors.lastname: Amellal
authors.forename: Armin
authors.initials: A
authors.lastname: Schueler
authors.forename: Andreas
authors.initials: A
authors.lastname: Harstrick
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; 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; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil