title: Activity and safety of bevacizumab plus fotemustine for recurrent malignant gliomas.
abstract: BACKGROUND
  No established chemotherapeutic regimen exists for the treatment of recurrent malignant gliomas (rMGs). Herein, we report the activity and safety results of the bevacizumab (B) plus fotemustine (FTM) combination for the treatment of rMGs.
  
  
  METHODS
  An induction phase consisted of B 10 mg/kg days 1, 15 plus FTM 65 mg/m(2) days 1, 8, and 15. Nonprogressive patients entered the maintenance phase with B 10 mg/kg plus FTM 75 mg/m(2) every 3 weeks. The primary endpoint was response rate; secondary endpoints included safety, progression free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Twenty-six patients affected by recurrent MGs (50% glioblastoma) were enrolled. Eight partial responses (31%) were observed. Median PFS and OS were 4 (95% C.I.: 2.8-5.1) and 6 months (95% C.I.: 4.2-7.8), respectively. Responses were significantly associated with both improved PFS and OS (P = 0.002 and P = 0.001, resp.). Treatment adverse events were mostly mild to moderate in intensity. Bevacizumab-related adverse events included grade 3 venous thromboembolic event (8%), grade 2 epistaxis (4%), hypertension (8%), and gastrointestinal perforation (4%).
  
  
  CONCLUSIONS
  Bevacizumab plus FTM showed activity and good tolerability in pretreated MGs. Further investigations are needed in order to verify the benefits deriving from the addition of B to a cytotoxic in this clinical setting of patients.
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Vaccaro
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Diagnostic Oncology Department, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vidiri
authors.affiliation: Biostatistic Unit, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Division of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Metro
authors.affiliation: Division of Neurosurgery, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Telera
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Vari
authors.affiliation: Diagnostic Oncology Department, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piludu
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Carosi
authors.affiliation: Division of Neurology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Villani
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cognetti
authors.affiliation: Division of Neurosurgery, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pompili
authors.affiliation: Department of Radiation Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marucci
authors.affiliation: Division of Neurosurgery, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: C M
authors.initials: CM
authors.lastname: Carapella
authors.affiliation: Division of Neurology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pace
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D000068258:Bevacizumab; C054368:fotemustine