title: Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study.
abstract: OBJECTIVE
  Vascular endothelial growth factor is a key promoter of tumor progression in cervical carcinoma. The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of bevacizumab, a recombinant humanized anti-vascular endothelial growth factor monoclonal antibody.
  
  
  METHODS
  Eligible patients had recurrent cervical cancer, measurable disease, and GOG performance status < or = 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and toxicity.
  
  
  RESULTS
  Forty-six patients were enrolled (median age, 46 years); 38 patients (82.6%) received prior radiation as well as either one (n = 34, 73.9%) or two (n = 12, 26.1%) prior cytotoxic regimens for recurrent disease. Grade 3 or 4 adverse events at least possibly related to bevacizumab included hypertension (n = 7), thrombo-embolism (n = 5), GI (n = 4), anemia (n = 2), other cardiovascular (n = 2), vaginal bleeding (n = 1), neutropenia (n = 1), and fistula (n = 1). One grade 5 infection was observed. Eleven patients (23.9%; two-sided 90% CI, 14% to 37%) survived progression free for at least 6 months, and five patients (10.9%; two-sided 90% CI, 4% to 22%) had partial responses. The median response duration was 6.21 months (range, 2.83 to 8.28 months). The median PFS and overall survival times were 3.40 months (95% CI, 2.53 to 4.53 months) and 7.29 months (95% CI, 6.11 to 10.41 months), respectively. This compared favorably with historical phase II GOG trials in this setting. CONCLUSION Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer and merits phase III investigation.
authors.affiliation: University of California, Irvine Medical Center, Bldg 56, Room 262, 101 The City Dr, Orange, CA 92868. USA. bjmonk@uci.edu
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Gray
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Buekers
authors.forename: Lynda D
authors.initials: LD
authors.lastname: Roman
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016879:Salvage Therapy; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab