title: Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer.
abstract: OBJECTIVE
  We evaluated the efficacy and safety of bevacizumab in patients with platinum-resistant epithelial ovarian carcinoma (EOC) or peritoneal serous carcinoma (PSC) who had experienced disease progression during, or within 3 months of discontinuing, topotecan or liposomal doxorubicin.
  
  
  METHODS
  No more than three prior treatment regimens were allowed. Patients received single-agent bevacizumab 15 mg/kg intravenously every 3 weeks. Response was assessed by computed tomography (CT) scan every 6 weeks using Response Evaluation Criteria in Solid Tumors (RECIST).
  
  
  RESULTS
  Of 44 patients treated, 83.7% were primarily platinum resistant, 59.1% had received liposomal doxorubicin, 25% topotecan, 15.9% both agents, and 47.7% had received three prior chemotherapy regimens. A median of five (range, two to 16) bevacizumab doses were administered. Partial responses were observed in seven patients (15.9%). Median progression-free survival was 4.4 months (95% CI, 3.1 to 5.5 months), with a median survival duration of 10.7 months at study termination. Bevacizumab-associated grade 3 to 4 events included hypertension (9.1%), proteinuria (15.9%), bleeding (2.3%), and wound-healing complications (2.3%). The incidence of GI perforation (GIP; 11.4%) was higher than reported in bevacizumab trials of other tumor types. GIP occurred in 23.8% of patients receiving three prior chemotherapy regimens, compared with 0% of patients receiving two prior chemotherapy regimens (P < .01). A trend toward higher risk of GIP was observed for patients with bowel wall thickening or bowel obstruction on CT scan. Arterial thromboembolic events occurred in three patients (6.8%). Three deaths were related to bevacizumab treatment.
  
  
  CONCLUSIONS
  Bevacizumab has single-agent activity in patients with platinum-resistant EOC or PSC. A higher than expected incidence of GIP was noted in these heavily pretreated patients.
authors.affiliation: Beth Israel Deaconess Medical Center, East Campus KS158, 330 Brookline Ave, Boston, MA 02215, USA. scannist@bidmc.harvard.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Cannistra
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
authors.forename: Julie
authors.initials: J
authors.lastname: Hambleton
authors.forename: Jakob
authors.initials: J
authors.lastname: Dupont
authors.forename: Howard
authors.initials: H
authors.lastname: Mackey
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Douglas
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: Deborah
authors.initials: D
authors.lastname: Armstrong
authors.forename: Robert
authors.initials: R
authors.lastname: Wenham
authors.forename: William
authors.initials: W
authors.lastname: McGuire
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007416:Intestinal Perforation / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab