title: Bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer.
abstract: OBJECTIVE
  To retrospectively assess the efficacy and safety of bevacizumab plus low-dose metronomic oral cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer.
  
  
  METHODS
  Patients with recurrent ovarian cancer and prior treatment with platinum- and taxane-based chemotherapy were included. Treatment consisted of bevacizumab 10 mg/kg intravenously every 2 weeks plus oral cyclophosphamide 50 mg daily until disease progression or unacceptable toxicity. Response rates (RR) were determined according to RECIST criteria and by monitoring the CA 125 serum tumor marker according to Rustin's criteria. The endpoints were progression-free survival (PFS), RR, overall survival (OS), and safety.
  
  
  RESULTS
  Thirty-eight patients were treated; 79% were platinum resistant and 21% were platinum sensitive. The median number of previous treatments was 4 (range 1-8). Seventy-nine percent of patients had received more than 2 previous lines of treatment. Eighty-one percent of patients had received gemcitabine, 76% liposomal doxorubicin, and 50% topotecan. A median of 8 (range 1-70) cycles of bevacizumab were administered. The overall RR was a complete response (CR) in 3 patients (8.1%), a partial response (PR) in 12 (32.4%), and stable disease (SD) ≥6 months in 3 (8.1%). The median PFS and OS were 4.5 and 10.7 months, respectively. Thirty-nine percent of patients were progression free for at least 6 months. In an exploratory analysis there was a significant relation of prior platinum response and performance status with the risk of progression. Grade 3-4 toxicities included anemia (1), hypertension (2), hematuria (1), arterial thrombosis in the leg (1), dyspnea (1), and intestinal fistulae (1). There were no cases of gastrointestinal perforation (GIP) or treatment-related deaths.
  
  
  CONCLUSIONS
  The combination of bevacizumab and metronomic cyclophosphamide was active and well-tolerated in heavily pretreated patients with recurrent ovarian cancer.
authors.affiliation: Servicio de Oncología Médica, Hospital Universitario Virgen de la Victoria, Málaga, España. asmoncomed@yahoo.es
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sánchez-Muñoz
authors.forename: César
authors.initials: C
authors.lastname: Mendiola
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pérez-Ruiz
authors.forename: César A
authors.initials: CA
authors.lastname: Rodríguez-Sánchez
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Jurado
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alonso-Carrión
authors.forename: Ismael
authors.initials: I
authors.lastname: Ghanem
authors.forename: Guillermo
authors.initials: G
authors.lastname: de Velasco
authors.forename: Cristina
authors.initials: C
authors.lastname: Quero-Blanco
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018269:Carcinoma, Endometrioid / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016016:Proportional Hazards Models; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003520:Cyclophosphamide