title: Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology).
abstract: 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.
authors.affiliation: Dept. Neuro-Oncology, University and City of Health and Science Hospital of Turin, Via Cherasco 15, 10126, Turin, Italy, riccardo.soffietti@unito.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Soffietti
authors.forename: Elisa
authors.initials: E
authors.lastname: Trevisan
authors.forename: Luca
authors.initials: L
authors.lastname: Bertero
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
authors.forename: Isabella
authors.initials: I
authors.lastname: Morra
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Fabrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasqualetti
authors.forename: Ivan
authors.initials: I
authors.lastname: Lolli
authors.forename: Anna
authors.initials: A
authors.lastname: Castiglione
authors.forename: Giovannino
authors.initials: G
authors.lastname: Ciccone
authors.forename: Roberta
authors.initials: R
authors.lastname: Rudà
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009460:Neurologic Examination; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D025521:Tumor Suppressor Proteins; D000068258:Bevacizumab; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; C054368:fotemustine