Bevacizumab for Patients with Recurrent Multifocal Glioblastomas

Abstract

In patients with glioblastoma, antiangiogenic therapy with bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall survival (OS). Especially in patients with an unusual infiltrative phenotype as seen in multifocal glioblastoma, the use of BEV therapy is still more controversial. Therefore, we prepared a retrospective case series with 16 patients suffering from a multifocal glioblastoma treated with BEV. We compared these patients to a matched control cohort of 16 patients suffering from glioblastoma with a single lesion treated with BEV. The objective of this study was to evaluate whether the course of disease differs in glioblastoma patients with a multifocal disease pattern compared to those with a single lesion only. Patients were treated with BEV monotherapy or BEV in combination with irinotecan or lomustine (CCNU). Response rates and PFS were similar in both groups. There was a trend for an unfavorable OS in the patient group with multifocal glioblastoma, which was expected due to the generally worse prognosis of multifocal glioblastoma. We investigated whether BEV therapy affects the invasive growth pattern as measured by the appearance of new lesions on magnetic resonance imaging (MRI). Under BEV therapy, there was a trend for a lower frequency of new lesions both in multifocal and solitary glioblastoma. Based on these results, BEV therapy at relapse appears to be justified to no lesser extent in multifocal glioblastoma than in solitary glioblastoma.

Non-methylated MGMT as Predictive Factor in Newly Diagnosed Glioblastoma Multiforme Treated with Bevacizumab Concurrent with Radiotherapy Followed by Adjuvant Bevacizumab plus Irinotecan versus Temozolomide Concurrent with Radiotherapy Followed by Adjuvant Temozolomide

“…Bevacizumab (BEV) is a monoclonal humanized antibody of the immunoglobulin G1 (IgG1) against VEGF-A was developed, inhibiting neovascularization and reducing vascular permeability then reducing focal brain edema [10]. In recurrent glioblastome multiforme, a progression free survival benefit but not overall survival benefit was reported with bevacizumab from several non-randomized trials [11,12]. As first line setting the same results were reported as improved progression free survival but not overall survival [13,14].…”

Standard awake surgery versus hypnosis aided awake surgery for the management of high grade gliomas: A non-randomized cohort comparison controlled trial

“…While radiotherapy with concomitant and adjuvant temozolomide is the standard treatment after surgery in GBM patients, several institutions 17 have studied on prolonged administration of temozolomide and show increased survival periods of these patients or the use of Bevacizumab has similar effects in patients with mfGBM as compared to patients with GBM with single lesion. 16 The whole brain should be considered as the clinical target volume and, because of the diffuse infiltration, seems to be the most relevant area to achieve irradiation of all of the microscopic disease. 20 Radiation therapy fields, too, have the potential to be affected by a molecular signature.…”

The Brain Penetrating and Dual TORC1/TORC2 Inhibitor, RES529, Elicits Anti-Glioma Activity and Enhances the Therapeutic Effects of Anti-Angiogenetic Compounds in Preclinical Murine Models

“…Several inhibitors of PI3K/Akt/mTOR pathways have been developed for the treatment of different cancers including GBM. Clinical trials using rapamycin analogs were found to display insufficient anti-tumor activity in patients with rGBM [48,57,58,59]. A possibility could be the heterogeneity of GBM, with its redundant signaling inputs and ability to bypass blockade of individual molecules through compensatory feedback loops.…”

“…BEVA is responsible for vascular regression, tumor growth inhibition, and prolonged survival suggesting that this agent shows antitumor effects. There are evidences on direct antitumor effects of BEVA on established GBM and glioma stem-like cells [5,57,58,59,60] and BEVA shows significant anti-tumor potential as monotherapy [61]. It has also been demonstrated that BEVA monotherapy was associated with increased in intra-tumor AKT phosphorylation levels [62].…”