title: Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group.
abstract: OBJECTIVE
  To evaluate the feasibility, toxicity, and efficacy of single-agent monoclonal antibody therapy targeting the human epidermal growth factor receptor 2 (HER2)/neu receptor in ovarian and primary peritoneal carcinoma.
  
  
  METHODS
  Eligible patients had measurable persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with 2+ or 3+ HER2 overexpression documented by immunohistochemistry. Intravenous trastuzumab was administered initially at a dose of 4 mg/kg, then weekly at 2 mg/kg. Patients without progressive disease or excessive toxicity could continue treatment indefinitely. Those with stable or responding disease at 8 weeks were offered treatment at a higher weekly dose (4 mg/kg) at time of progression. Patient sera were analyzed for the presence of the soluble extracellular domain of HER2, host antibodies against trastuzumab, and trastuzumab pharmacokinetics.
  
  
  RESULTS
  A total of 837 tumor samples were screened for HER2 expression, and 95 patients (11.4%) exhibited the requisite 2+/3+ expression level. Forty-five patients, all of whom received prior chemotherapy, were entered, and 41 were deemed eligible and assessable. There were only mild expected toxicities and no treatment-related deaths. Although an elevated level of the soluble extracellular domain of HER2 was detected in eight of 24 patients, serum HER2 was not associated with clinical outcome. There was no evidence of host antitrastuzumab antibody formation. Serum concentrations of trastuzumab gradually increased with continued therapy. An overall response rate of 7.3% included one complete and two partial responses. Median treatment duration was 8 weeks (range, 2 to 104 weeks), and median progression-free interval was 2.0 months.
  
  
  CONCLUSIONS
  The clinical value of single-agent trastuzumab in recurrent ovarian cancer is limited by the low frequency of HER2 overexpression and low rate of objective response among patients with HER2 overexpression.
authors.affiliation: Division of Medical Science, Fox Chase Cancer Center, Rockledge, PA, USA. ma_bookman@fccc.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bookman
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Daniel
authors.initials: D
authors.lastname: Clarke-Pearson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Boothby
authors.forename: Ira R
authors.initials: IR
authors.lastname: Horowitz
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab