Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO Italian Association of Neuro-OncologyReport as inadecuate

Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO Italian Association of Neuro-Oncology - Download this document for free, or read online. Document in PDF available to download.

Journal of Neuro-Oncology

, Volume 116, Issue 3, pp 533–541

First Online: 01 December 2013Received: 03 September 2013Accepted: 17 November 2013DOI: 10.1007-s11060-013-1317-x

Cite this article as: Soffietti, R., Trevisan, E., Bertero, L. et al. J Neurooncol 2014 116: 533. doi:10.1007-s11060-013-1317-x


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.

KeywordsBevacizumab Fotemustine Nitrosoureas Glioblastoma Recurrence  Download fulltext PDF

Author: Riccardo Soffietti - Elisa Trevisan - Luca Bertero - Paola Cassoni - Isabella Morra - Maria Grazia Fabrini - Francesco Pas


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