title: Phase II study of cisplatin plus cetuximab in advanced, recurrent, and previously treated cancers of the cervix and evaluation of epidermal growth factor receptor immunohistochemical expression: a Gynecologic Oncology Group study.
abstract: BACKGROUND
  The purpose of this study was to evaluate the safety and efficacy of cetuximab (C225), an antibody that inhibits epidermal growth factor receptor (EGFR) activity, with cisplatin and to explore associations between EGFR protein expression with patient demographics or clinical outcome.
  
  
  METHODS
  Women with advanced, persistent, or recurrent carcinoma of the cervix were eligible. The women received cisplatin at 30mg/m(2) on days 1 and 8 with a loading dose of cetuximab at 400mg/m(2) followed by 250mg/m(2) on days 1, 8, and 15 in a 21day cycle. Adverse events were assessed with CTCAE v 3.0. Primary measure of efficacy was tumor response by RECIST. The study was stratified by prior chemotherapy (CT). EGFR protein expression in pre-treatment tumor was analyzed by immunohistochemistry.
  
  
  RESULTS
  Between September 2004 and March 2008, 76 patients were enrolled. Of these, 69 were eligible and evaluable; 44 (64%) received prior chemotherapy. There were 4 responses in each group, prior chemotherapy and no chemotherapy, 9% and 16%, respectively. Grade 4 toxicities included anemia (1), allergy (1), metabolic (1), and vascular (1). The most common grade 3 toxicities were metabolic (15), dermatologic (8), fatigue (6), and gastrointestinal (6). EGFR protein was expressed in 47/48 (98%) of tumors analyzed with a median cellular expression of 81%. Exploratory analyses revealed a trend between the percentage of cells expressing EGFR protein and PFS (hazard ratio=1.76, 95% confidence interval=0.96-3.21).
  
  
  CONCLUSIONS
  The combination of cetuximab with cisplatin was adequately tolerated but did not indicate additional benefit beyond cisplatin therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. john.farley@us.army.mil
authors.forename: John
authors.initials: J
authors.lastname: Farley
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: Michael
authors.initials: M
authors.lastname: Birrer
authors.forename: Joan
authors.initials: J
authors.lastname: Walker
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Schilder
authors.forename: J Tate
authors.initials: JT
authors.lastname: Thigpen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: Brigitte E
authors.initials: BE
authors.lastname: Miller
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068818:Cetuximab; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000201:enzymology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin