title: Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash.
abstract: OBJECTIVE
  Determine if cetuximab dose escalation to induce grade 2 rash correlates with anti-tumor activity and if sera-based markers could predict likelihood of response.
  
  
  METHODS
  Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m(2), then 250 mg/m(2) weekly for two 3-week cycles. Patients who had stable disease (SD) and <grade 2 rash were dose escalated in 75 mg/m(2) increments every 3 weeks until grade 2 rash or to a maximum weekly dose of 400 mg/m(2). Pre- and post-treatment serum samples were evaluated for potential predictive markers of response.
  
  
  RESULTS
  One of 25 patients achieved partial remission (PR) and 9 patients had SD. The median progression free survival was 2.1 months; the 1-year survival rate was 54.8%. Rash (96%) was the most common drug-related adverse event. At first response assessment, 4 patients remained at 250 mg/m(2); 8 patients were dose-escalated to 325 mg/m(2); of these, 4 ultimately were increased to 400 mg/m(2). Patients with progressive disease (PD) were removed from the study. Ninety-two serologic markers were analyzed from 20 patients to identify markers associated with clinical activity and/or predictive of outcome. Pretreatment levels of twelve markers were significantly elevated in patients exhibiting PD versus SD or PR; however, changes in marker levels during the course of treatment were not significant indicators of response.
  
  
  CONCLUSIONS
  Single-agent cetuximab showed minimal activity in patients with recurrent ovarian cancer. Patients with elevated levels of 12 serologic markers at baseline were more likely to have earlier disease progression.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. russell.schilder@fccc.edu
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Schilder
authors.forename: Harsh B
authors.initials: HB
authors.lastname: Pathak
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Holloway
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: Carol
authors.initials: C
authors.lastname: Aghajanian
authors.forename: Hua
authors.initials: H
authors.lastname: Min
authors.forename: Karthik
authors.initials: K
authors.lastname: Devarajan
authors.forename: Eric
authors.initials: E
authors.lastname: Ross
authors.forename: Charles W
authors.initials: CW
authors.lastname: Drescher
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
mesh_terms: D017486:Acneiform Eruptions / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood; D000068818:Cetuximab; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy*; D040901:Proteomics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068818:Cetuximab