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JOURNAL OF NEUROSURGICAL SCIENCES
A Journal on Neurosurgery
Indexed/Abstracted in: e-psyche, EMBASE, PubMed/MEDLINE, Neuroscience Citation Index, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,651
Journal of Neurosurgical Sciences 2016 Sep 28
Second line treatment of recurrent glioblastoma with sunitinib: results of a phase II study and systematic review of literature
Salvatore GRISANTI 1, Vittorio D. FERRARI 1, Michela BUGLIONE 2, Giorgio M. AGAZZI 1, Roberto LISERRE 3, Luigi POLIANI 4, Luciano BUTTOLO 5, Stefano GIPPONI 6, Rebecca PEDERSINI 1, Francesca CONSOLI 1, Pierpaolo PANCIANI 5, Elisa ROCA 1, Giannantonio SPENA 5, Luca TRIGGIANI 2, Alfredo BERRUTI 1, on behalf of the Gruppo Neuro-Oncologico Bresciano ✉
1 Department of Medical Oncology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 2 Department of Radiation Oncology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 3 Department of Neuroradiology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 4 Department of Pathology, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 5 Department of Neurosurgery, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 6 Department of Neurology, Spedali Civili di Brescia, University of Bescia, Brescia, Italy
INTRODUCTION: Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib (S) plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with S in this setting published to date and summarized it in a meta-analysis.
EVIDENCE ACQUISITION: Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with S 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon’s two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib.
EVIDENCE SYNTHESIS: Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-PFS was not reached. Therefore, the trial was stopped early for insufficient activity. All toxicities were grade 1-2. Systematic review of the literature identified 9 studies (including the present one) for a total of 221 patients. Pooled 6-PFS was 15.1% (95% CI 9.0-24.4). Subgroup analysis by different schedule revealed a 6-PFS of 17.5% (95% CI 10.3-28.1) in the weekly setting which was consistent across all the studies (I2 0%, p = 0.66) and a pooled 6-PFS of 12.7% (95% CI 4.9-29.1) in the daily setting with a substantial amount of heterogeneity (I2 65%, p = 0.01).
CONCLUSIONS: Results of this trial and those of the systematic review indicate that, compared to conventional chemotherapy or bevacizumab, S has insufficient activity in the setting of recurrent GBM. Better patient’s molecular stratification for second-line treatment in GBM is warranted.