title: Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer.
abstract: OBJECTIVE
  Bevacizumab (BEV) is a humanized monoclonal antibody against vascular endothelial growth factor. We reviewed our experience with BEV in patients with recurrent advanced epithelial ovarian cancer who had failed multiple prior chemotherapeutic regimens.
  
  
  METHODS
  Thirty-two patients not participating in an ongoing clinical trial were treated with BEV (15 mg/kg every 3 weeks IV). Demographic and clinicopathologic data, clinical outcomes, and adverse events were extracted from patient charts. RECIST and CA-125 Rustin criteria were retrospectively applied to evaluate response and progression. Median progression-free survival (PFS) and overall survival (OS) were determined using Kaplan-Meier methods. Adverse events were retrospectively categorized using the common terminology criteria for adverse events version 3.
  
  
  RESULTS
  The median patient age was 57 years (range 35-80) with 84% being Caucasian and 50% having a GOG performance status of 2. FIGO stages included 80% stage III and 10% stage IV. The tumors were mostly grades 2 (29%) and 3 (64%) and serous histological subtype (69%). All patients had failed multiple prior cytotoxic chemotherapies (median of 5 (range 2-10)) prior to BEV. The median duration of follow-up was 4.8 months (range 0.4-16.3). Twenty-three patients were treated with BEV alone, 2 received BEV with another chemotherapy regimen (5-FU/lecovorin plus oxaliplatin, cyclophosphamide), and 8 initially received BEV alone, followed by BEV with capcitabine, cyclophosphamide, docetaxel, carboplatin, or weekly paclitaxel. A median of 6 cycles (range 1-20) with 196 total doses of BEV was administered. One patient was lost to follow-up after cycle 1. We observed a 16% response rate (all in those treated with BEV alone) with 62.5% of patients demonstrating stable disease. Median OS was 6.9 months, and the median PFS was 5.5 months. Three grade 3 and no grade 4 adverse events were observed. Grade 3 toxicities included hypertension, proteinuria, and enterocutaneous fistula. The fistula occurred after 5 cycles of BEV in a patient who had undergone 7 debulking surgeries prior to BEV.
  
  
  CONCLUSIONS
  BEV is generally well tolerated after multiple prior cytotoxic regimens and results in significant clinical benefit among women with recurrent ovarian cancer.
authors.affiliation: Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California-Irvine Medical Center, 1012 The City Drive, Orange, CA 92868, USA. bjmonk@uci.edu
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Monk
authors.forename: Ernest
authors.initials: E
authors.lastname: Han
authors.forename: Carol A
authors.initials: CA
authors.lastname: Josephs-Cowan
authors.forename: Gordon
authors.initials: G
authors.lastname: Pugmire
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000628:therapy*; D016879:Salvage Therapy
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab