Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology)

J Neurooncol. 2014 Feb;116(3):533-41. doi: 10.1007/s11060-013-1317-x. Epub 2013 Dec 1.


The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6% (95% CI 29.3-55.2) and a median PFS of 5.2 months (95% CI 3.8-6.6). The median OS was 9.1 months (95% CI 7.3-10.3). Twenty-eight patients (52%) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60%). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76%), while the diffuse non-enhancing progression accounted for 9.5%. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22%) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4%) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab
  • Brain Neoplasms / drug therapy*
  • DNA Methylation / drug effects
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / metabolism
  • Female
  • Glioblastoma / drug therapy*
  • Humans
  • Italy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neurologic Examination
  • Nitrosourea Compounds / therapeutic use*
  • Organophosphorus Compounds / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Time Factors
  • Tumor Suppressor Proteins / metabolism


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Nitrosourea Compounds
  • Organophosphorus Compounds
  • Tumor Suppressor Proteins
  • Bevacizumab
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • fotemustine