title: Platinum-based chemotherapy plus cetuximab in head and neck cancer.
abstract: BACKGROUND
  Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
  
  
  METHODS
  We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first.
  
  
  RESULTS
  Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracil) significantly prolonged the median overall survival from 7.4 months in the chemotherapy-alone group to 10.1 months in the group that received chemotherapy plus cetuximab (hazard ratio for death, 0.80; 95% confidence interval, 0.64 to 0.99; P=0.04). The addition of cetuximab prolonged the median progression-free survival time from 3.3 to 5.6 months (hazard ratio for progression, 0.54; P<0.001) and increased the response rate from 20% to 36% (P<0.001). The most common grade 3 or 4 adverse events in the chemotherapy-alone and cetuximab groups were anemia (19% and 13%, respectively), neutropenia (23% and 22%), and thrombocytopenia (11% in both groups). Sepsis occurred in 9 patients in the cetuximab group and in 1 patient in the chemotherapy-alone group (P=0.02). Of 219 patients receiving cetuximab, 9% had grade 3 skin reactions and 3% had grade 3 or 4 infusion-related reactions. There were no cetuximab-related deaths.
  
  
  CONCLUSIONS
  As compared with platinum-based chemotherapy plus fluorouracil alone, cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00122460.)
authors.affiliation: Antwerp University Hospital, Department of Medical Oncology, Edegem, Belgium. jan.b.vermorken@uza.be
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: Ricard
authors.initials: R
authors.lastname: Mesia
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Eva
authors.initials: E
authors.lastname: Remenar
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kawecki
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rottey
authors.forename: Jozsef
authors.initials: J
authors.lastname: Erfan
authors.forename: Dmytro
authors.initials: D
authors.lastname: Zabolotnyy
authors.forename: Heinz-Roland
authors.initials: HR
authors.lastname: Kienzer
authors.forename: Didier
authors.initials: D
authors.lastname: Cupissol
authors.forename: Frederic
authors.initials: F
authors.lastname: Peyrade
authors.forename: Marco
authors.initials: M
authors.lastname: Benasso
authors.forename: Ihor
authors.initials: I
authors.lastname: Vynnychenko
authors.forename: Dominique
authors.initials: D
authors.lastname: De Raucourt
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Armin
authors.initials: A
authors.lastname: Schueler
authors.forename: Nadia
authors.initials: N
authors.lastname: Amellal
authors.forename: Ricardo
authors.initials: R
authors.lastname: Hitt
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D000068818:Cetuximab; D002945:Cisplatin; D005472:Fluorouracil