title: Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer.
abstract: OBJECTIVE
  Test the safety and efficacy of sequentially blocking angiogenesis by adding oral cyclophosphamide to bevacizumab following cancer progression on bevacizumab in patients with recurrent ovarian cancer.
  
  
  METHODS
  Eligibility included ≤ 2 lines of treatment for recurrence and measurable cancer by RECIST 1.0. Patients received bevacizumab (15 mg/kg every 3 weeks IV) and upon RECIST progression, oral cyclophosphamide (50mg orally daily) was added. Objectives included safety, toxicities, 3- and 6-month PFS rates, response rate, PFS, and OS.
  
  
  RESULTS
  20 patients were enrolled. Overall response rate was 10%, and 65% of patients had confirmed stable disease (SD). Thirteen of 20 patients received oral cyclophosphamide added to bevacizumab upon bevacizumab progression. Of these 13 patients, 1 patient subsequently achieved a PR (this patient had SD as best response during bevacizumab) and 3 patients had a confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS rate was 65%, duration of response (DOR) was 7.3 months, and median OS was 22.72 months. Median DOR for patients receiving both bevacizumab and cyclophosphamide was 8.4 months. Most toxicities were grades 1 and 2 and manageable. Grades 3 and grade 4 toxicities included 1 myocardial infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients (60%) developed grade 3 HTN.
  
  
  CONCLUSIONS
  Addition of oral cyclophosphamide to bevacizumab at the time of cancer progression on bevacizumab appears to have continued anti-cancer effects in a subgroup of patients and appears to be safe. Randomized trials testing combination versus sequential anti-angiogenic therapy for recurrent ovarian cancer are warranted.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: Lauren
authors.initials: L
authors.lastname: Pereira
authors.forename: Joyce
authors.initials: J
authors.lastname: Liu
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Julie
authors.initials: J
authors.lastname: Lee
authors.forename: Christin
authors.initials: C
authors.lastname: Whalen
authors.forename: Susana
authors.initials: S
authors.lastname: Campos
authors.forename: Tina
authors.initials: T
authors.lastname: Atkinson
authors.forename: Margaret
authors.initials: M
authors.lastname: Hill
authors.forename: Suzanne
authors.initials: S
authors.lastname: Berlin
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide