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      Bevacizumab for glioblastoma

      Therapeutics and Clinical Risk Management

      Dove Medical Press

      bevacizumab, glioblastoma, glioma, adverse events

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          Abstract

          Individuals with glioblastoma are often characterized by older age, advanced neurologic manifestations at the primary stage, and unresectable tumors, and these factors are associated with poor treatment outcomes. Administration of bevacizumab (BV, Avastin ®) promotes tumor regression and improves cerebral edema, and is expected to improve neurologic findings in many patients with malignant gliomas, including glioblastoma. Although the addition of BV to the conventional standard therapy (chemoradiotherapy with temozolomide) for newly diagnosed glioblastoma prolonged the progression-free survival time and the performance status of patients, it failed to extend overall survival time. However, more than 50% of glioblastoma patients show Karnofsky performance status ≤70 at initial presentation; therefore, BV should be used to improve or maintain their performance status as an initial treatment. Most of the adverse events of BV, except hypertension and proteinuria, occur as complications of glioblastoma, and explanation of the advantages and disadvantages of BV administration to patients is important. Herein, the efficacy, safety, and challenges of using BV for treating glioblastoma were reviewed.

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          Most cited references 59

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          Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

          Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.
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            Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.

            The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.
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              Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial.

              Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear. We report the results of the first randomised controlled phase 2 trial of bevacizumab in recurrent glioblastoma.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                01 December 2015
                : 11
                : 1759-1765
                Affiliations
                Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan
                Author notes
                Correspondence: Yoshitaka Narita, Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, Tel +81 3 3542 2511, Fax +81 3 3542 2551, Email yonarita@ 123456ncc.go.jp
                Article
                tcrm-11-1759
                10.2147/TCRM.S58289
                4671800
                © 2015 Narita. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Medicine

                adverse events, glioma, glioblastoma, bevacizumab

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