title: Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study.
abstract: OBJECTIVE
  Therapy of recurrent/metastatic squamous cell carcinoma of the head and neck results in median progression-free survival (PFS) of 2 months. These cancers are rich in epidermal growth factor receptor (EGFR). We wished to determine whether the addition of cetuximab, which inhibits activation of EGFR, would improve PFS.
  
  
  METHODS
  Patients with recurrent/metastatic squamous cell carcinoma of the head and neck were randomly assigned to receive cisplatin every 4 weeks, with weekly cetuximab (arm A) or placebo (arm B). Tumor tissue was assayed for EGFR expression by immunohistochemistry. The primary end point was PFS. Secondary end points of interest were response rate, toxicity, overall survival, and correlation of EGFR with clinical end points.
  
  
  RESULTS
  There were 117 analyzable patients enrolled. Median PFS was 2.7 months for arm B and 4.2 months for arm A. The hazard ratio for progression of arm A to arm B was 0.78 (95% CI, 0.54 to 1.12). Median overall survival was 8.0 months for arm B and 9.2 months for arm A (P = .21). The hazard ratio for survival by skin toxicity in cetuximab-treated patients was 0.42 (95% CI, 0.21 to 0.86). Objective response rate was 26% [corrected] for arm A and 10% [corrected] for arm B (P = .03). Enhancement of response was greater for patients with EGFR staining present in less than 80% of cells.
  
  
  CONCLUSIONS
  Addition of cetuximab to cisplatin significantly improves response rate. There was a survival advantage for the development of rash. Progression-free and overall survival were not significantly improved by the addition of cetuximab in this study.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. barbara.burtness@fccc.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Burtness
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Goldwasser
authors.forename: William
authors.initials: W
authors.lastname: Flood
authors.forename: Bassam
authors.initials: B
authors.lastname: Mattar
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Forastiere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012720:Severity of Illness Index; D012871:Skin Diseases / Q000139:chemically induced; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin