Abstract：
:Antiangiogenic therapies for malignant gliomas often result in transient response, and recurrent disease is characterized by adoption of invasive and hypoxic phenotype. The notch signaling pathway is activated in gliomas, and augments cell migration and hypoxic response. Here we report a clinical study of the combination of bevacizumab and RO4929097, an inhibitor of the notch signaling cascade. A phase I clinical trial was conducted through the Adult Brain Tumor Consortium in subjects with recurrent malignant glioma. Primary objectives were to assess safety and to define the maximum tolerated dose of RO4929097 in combination with bevacizumab. Secondary objectives were to determine overall survival, progression free survival, radiographic response, pharmacokinetic evaluation, and tissue biomarker analysis. Thirteen subjects were enrolled. Of the three subjects treated with the highest dose of RO4929097, one grade 3 toxicity and one grade 2 toxicity were observed. Definitive maximum tolerated dose of RO4929097 in combination with bevacizumab was not identified due to manufacturer's decision to halt drug production. 2 of 12 evaluable subjects demonstrated radiographic response; one subject experienced CR and the second PR. The median overall survival was 10.9 months with a median progression-free survival of 3.7 months. Two subjects remained free of disease progression at 6 months from treatment initiation. PK evaluation did not identify clinically significant drug-drug interactions. All analyzed tissue specimens revealed activation of notch signaling. Combination of RO4929097 and bevacizumab was well-tolerated. Given the compelling scientific rationale, additional studies of antiangiogenic and notch signaling inhibitors should be considered.
journal_name
J Neurooncoljournal_title
Journal of neuro-oncologyauthors
Pan E,Supko JG,Kaley TJ,Butowski NA,Cloughesy T,Jung J,Desideri S,Grossman S,Ye X,Park DMdoi
10.1007/s11060-016-2263-1subject
Has Abstractpub_date
2016-12-01 00:00:00pages
571-579issue
3eissn
0167-594Xissn
1573-7373pii
10.1007/s11060-016-2263-1journal_volume
130pub_type
杂志文章abstract：:Twenty-eight patients with malignant brain tumors (16 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation with or without chemotherapy received varying doses of intracarotid VP-16. Courses of therapy were repeated every 4 weeks along with computerized axial tomography scan and...
journal_title：Journal of neuro-oncology
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doi：10.1007/BF00195611
更新日期：1987-01-01 00:00:00
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journal_title：Journal of neuro-oncology
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,评审
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doi：10.1007/s11060-010-0444-x
更新日期：2011-07-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,评审
doi：10.1007/BF01053420
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/BF02427837
更新日期：1990-10-01 00:00:00
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journal_title：Journal of neuro-oncology
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更新日期：2009-07-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,评审
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更新日期：2006-05-01 00:00:00
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更新日期：2015-02-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-004-2061-z
更新日期：2005-04-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
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更新日期：2005-05-01 00:00:00
abstract：PURPOSE:To analyze patterns of failure according to treatment modalities and evaluate the adequacy of an institution's current volume of postoperative radiotherapy (PORT) for World Health Organization (WHO) grade II or III meningiomas. PATIENTS AND METHODS:Data of 98 patients treated by either surgery and PORT (PORT g...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-019-03232-w
更新日期：2019-09-01 00:00:00
abstract：:Leiomyosarcoma has recently been identified as an AIDS-related tumor, usually occurring in children in the chest or abdomen. We describe a case of intracranial leiomyosarcoma in an adult with AIDS. An enhancing mass adjacent to the right occipital cortical surface was diagnosed during a work-up for left arm weakness. ...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
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更新日期：2014-06-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1023/a:1016226319068
更新日期：2002-07-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,评审
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更新日期：2006-12-01 00:00:00
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journal_title：Journal of neuro-oncology
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更新日期：2014-04-01 00:00:00
abstract：INTRODUCTION:There has been a resurgence of interest in brachytherapy as a treatment for glioblastoma, with several currently ongoing clinical trials. To provide a foundation for the analysis of these trials, we analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine whether receipt of brac...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-019-03268-y
更新日期：2019-10-01 00:00:00
abstract：:Autologous brain tumor specific CTLs were induced from the patient's PBL by a mixed lymphocyte-tumor culture, and were maintained for more than 2 months in a medium containing exogenous IL-2. The autologous T cell line containing specific CTL was administered into the tumor-bed for the treatment of malignant glioma. I...
journal_title：Journal of neuro-oncology
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doi：10.1007/BF00195603
更新日期：1987-01-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章,评审
doi：10.1007/BF01324700
更新日期：1993-05-01 00:00:00
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journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1023/a:1006124917643
更新日期：1999-01-01 00:00:00
abstract：:While stereotactic radiosurgery (SRS) has been shown effective in the management of brain metastases, small brain metastases (≤10 mm) can pose unique challenges. Our aim was to investigate the efficacy of SRS in the treatment of small brain metastases, as well as elucidate clinically relevant factors impacting local f...
journal_title：Journal of neuro-oncology
pub_type： 杂志文章
doi：10.1007/s11060-017-2519-4
更新日期：2017-09-01 00:00:00
