Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis

Background: Glioblastoma (GB) is the most common malignant primary central nervous system tumor in adults. Standard-of-care therapy includes surgical resection, radiotherapy and temozolomide, but nearly all patients experience disease progression. The purpose of this study was to describe 2 cohorts of patients with recurrent GB submitted to second-line treatment with procarbazine/lomustine/vincristine (PCV) or bevacizumab/irinotecan (BI). Material and Methods: Retrospective analysis of GB patients treated in our center with PCV or BI, after progression with temozolomide, between 2004 and 2012. Results: Among 60 patients, 41 were treated with BI and 19 with PCV. According to the Macdonald criteria, the overall response rate in the BI group was 66% (n = 27) while it was 11% (n = 2) in the PCV group. The median progression-free survival was 5 and 3 months in the BI and PCV group, respectively. The median overall survival (OS) since second-line chemotherapy was 9 months in the BI group and 5 months in the PCV group. The latter group had a worse toxicity profile (grade 3-4: 52.6% vs. 22.0%; grade 1-2: 89.5% vs. 68.3%). Conclusions: The BI cohort had higher response rates, almost twice the OS and a lower degree of toxicity in contrast to the PCV group. The small number of patients and historical cohorts limits these comparisons.

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“…Our results are similar to those described in the literature for bevacizumab-containing chemotherapy [15,17,18,19,20,21,22,23]. …”

Section: Discussionsupporting

confidence: 82%

“…The BI combination was well tolerated, and the incidence of targeted AEs was similar to those observed in previous trials [15,18,19,21,25,26]. The BI group experienced a higher incidence of venous thromboembolic events and the hematologic AEs were more frequent in the PCV-treated patients.…”

Section: Discussionsupporting

confidence: 62%

Second-Line Chemotherapy in Recurrent Glioblastoma: A 2-Cohort Study

et al. 2015

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“…New therapeutic approaches against these targets have the potential to be put into clinical treatment for tumors. Bevacizumab (a humanized monoclonal antibody) is an eVective anti-angiogenic agent that is the Wrst to be approved by the American Food and Drug Administration as the Wrst-line treatment for metastatic colorectal cancer (Ranieri et al 2006), and it blocks secreted VEGF and prolongs overall survival of patients with advanced NSCLC in combination with standard chemotherapy in a randomized phase 3 trial (Sandler et al 2006) and patients who respond well to Bevacizumab with recurrent malignant gliomas (Xu et al 2010). In our meta-analysis of 6 articles, we found a signiWcant positive association of elevated VEGF with the death of patients in the Wfth years after diagnosis, of which the pooled relative risk of "VEGF+" against "VEGF¡" was 2.85, which suggests a 2.85-fold higher 5-year mortality rate for osteosarcoma patients with the positive detection of VEGF.…”

Section: Discussionmentioning

confidence: 98%

The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review

Jian

Wang

et al. 2012

J Cancer Res Clin Oncol

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The prognostic significance of VEGF expression in all its isoforms is still unknown based on the limited data available, but we find VEGF165 may play an important role. Future studies should examine the relationship between VEGF isoform expression and patients' survival and the relationship between VEGF isoform expression and EMMPRIN expression, which could be helpful for predicting the prognosis of patients with osteosarcoma. Once the conclusion of whether the VEGF and its isoforms playing a role in osteosarcoma were reached, it would help guide clinical decision-making regarding therapy and outcomes. In addition, we recommend a >25% positive staining of the cells as a VEGF-positive cut-off value in immunohistochemistry, since we find a relatively strict detecting method is likely to yield significant result in the 5-year survival of patients.

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“…VEGF inhibition in human GBM results in dramatic reductions in gadolinium-enhancing lesions, suggesting a potential decrease in tumor vascular permeability [14,47]. Therefore, vascular permeability was assessed in GL261-bearing mice with and without aflibercept treatment.…”

Section: Inhibition Of Vegf Reduces Permeability and Promotes Normalimentioning

confidence: 99%

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

et al. 2016

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The addition of antiangiogenic therapy to the standard-of-care treatment regimen for recurring glioblastoma has provided some clinical benefits while also delineating numerous caveats, prompting evaluation of the elicited alterations to the tumor microenvironment. Of critical importance, given the steadily increasing incorporation of immunotherapeutic approaches clinically, is an enhanced understanding of the interplay between angiogenic and immune response pathways within tumors. In the present study, the GL261 glioma mouse model was used to determine the effects of antiangiogenic treatment in an immune-competent host. Following weekly systemic administration of aflibercept, an inhibitor of vascular endothelial growth factor, tumor volume was assessed by magnetic resonance imaging and changes to the tumor microenvironment were determined. Treatment with aflibercept resulted in reduced tumor burden and increased survival compared with controls. Additionally, decreased vascular permeability and preservation of the integrity of tight junction proteins were observed. Treated tumors also displayed hallmarks of anti-angiogenic evasion, including marked upregulation of vascular endothelial growth factor expression and increased tumor invasiveness. Aflibercept was then administered in combination with a picornavirusbased antitumor vaccine and tumor progression was evaluated. This combination therapy significantly delayed tumor progression and extended survival beyond that observed for either therapy alone. As such, this work demonstrates the efficacy of combined antiangiogenic and immunotherapy approaches for treating established gliomas and provides a foundation for further evaluation of the effects of antiangiogenic therapy in the context of endogenous or vaccine-induced inflammatory responses.

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Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis

Cited by 51 publications

References 43 publications

Second-Line Chemotherapy in Recurrent Glioblastoma: A 2-Cohort Study

Second-Line Chemotherapy in Recurrent Glioblastoma: A 2-Cohort Study

The prognostic value of elevated vascular endothelial growth factor in patients with osteosarcoma: a meta-analysis and systemic review

Improved Treatment Efficacy of Antiangiogenic Therapy when Combined with Picornavirus Vaccination in the GL261 Glioma Model

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