title: Phase II trial of cetuximab in patients with metastatic or locally advanced soft tissue or bone sarcoma.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) tyrosine kinase is overexpressed in many sarcoma subtypes. In vitro studies suggest a role of the EGFR pathway in growth and differentiation in some sarcomas. We conducted a phase II trial of cetuximab, a monoclonal antibody to EGFR, in patients with advanced sarcomas.
  
  
  METHODS
  Cetuximab was administered intravenously as a loading dose on 400 mg/m on day 1, cycle 1 and subsequently 250 mg/m on days 1, 8, 15, and 21 of a 28 day cycle. Using a Simon 2-stage design, 21 EGFR patients were to be accrued in the first stage, with an additional 11 patients if >3 patients met the primary endpoint of 4-month progression-free survival (PFS). An exploratory subgroup of EGFR patients was also included.
  
  
  RESULTS
  Twenty-one and 15 evaluable patients enrolled in the EGFR and EGFR subgroup, respectively. One of 21 EGFR patients (4.8%) achieved 4-month PFS. Median PFS and overall survival were 1.7 months [95% confidence interval (CI), 1.6-1.8] and 7.7 months (95% CI, 4.2-10.7), respectively. Three of 15 EGFR patients (20%) achieved 4-month PFS. Median PFS and overall survival were 1.8 months (95% CI, 0.8-2.5) and 15.7 months (95% CI, 7.7-25.3), respectively. No responses were seen in either group. There was no correlation between clinical outcomes and expression of MAP-K, PTEN, and phospho-EGFR.
  
  
  CONCLUSIONS
  Cetuximab is not an active as a single agent in advanced sarcoma. Further study of anti-EGFR therapy in sarcoma should only be considered after identification of molecular abnormalities predictive of benefit.
authors.affiliation: Moses Cone Reg Cancer Ctr., Greensboro, NC, USA.
authors.forename: Huan T
authors.initials: HT
authors.lastname: Ha
authors.forename: Kent A
authors.initials: KA
authors.lastname: Griffith
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Scott M
authors.initials: SM
authors.lastname: Schuetze
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: David R
authors.initials: DR
authors.lastname: Lucas
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
authors.forename: Rashmi
authors.initials: R
authors.lastname: Chugh
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000068818:Cetuximab; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab