title: Bevacizumab combination therapy in recurrent, platinum-refractory, epithelial ovarian carcinoma: A retrospective analysis.
abstract: BACKGROUND
  The study was undertaken to determine the safety and efficacy of the monoclonal, antivascular endothelial growth factor antibody bevacizumab in combination with cytotoxic chemotherapy for women with platinum-refractory ovarian cancer.
  
  
  METHODS
  A retrospective analysis of women who received bevacizumab in combination with a cytotoxic agent was performed. Response was determined by measurable disease or assessment of serial cancer antigen (CA) 125 measurements.
  
  
  RESULTS
  Twenty-three patients were identified. The patients were heavily pretreated with a median of 7 prior regimens including a median of 3 prior platinum regimens. The combination regimen included cyclophosphamide in 15 (65%), 5-fluorouracil (5-FU) in 6 (26%), docetaxel in 1 (4%), and gemcitibine/liposomal doxorubicin in 1 (4%). Two (9%) women developed chylous ascites during treatment. CTC Grade 4-5 toxicities occurred in 4 (17%) subjects. Gastrointestinal perforation occurred in 2 (9%) patients. Measurable disease was present in 22. The overall best response rate was 35% and all 8 were partial responses (PRs). Stable disease was found in a further 10 (44%) women, whereas progressive disease was observed in 5 (22%). The median time to progression was 5.6 months in patients with a PR and 2.3 months in subjects with stable disease. Three (13%) women experienced a progression-free interval (PFI) of >6 months. At last follow-up, 8 (35%) subjects had died of disease, whereas 15 (65%) women were alive with disease.
  
  
  CONCLUSIONS
  Combination bevacizumab therapy demonstrated activity in heavily pretreated women with ovarian cancer. Gastrointestinal perforations were identified in 9%. Despite the toxicity of the regimen, prospective studies, particularly in less heavily pretreated patients, are warranted.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. wrightj@msnotes.wustl.edu
authors.forename: Jason D
authors.initials: JD
authors.lastname: Wright
authors.forename: Andrea
authors.initials: A
authors.lastname: Hagemann
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rader
authors.forename: Dana
authors.initials: D
authors.lastname: Viviano
authors.forename: Randall K
authors.initials: RK
authors.lastname: Gibb
authors.forename: Lori
authors.initials: L
authors.lastname: Norris
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Powell
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017671:Platinum Compounds; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000068258:Bevacizumab; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D000093542:Gemcitabine