Abstract:
BACKGROUND:We report a phase I study to examine the pharmacokinetics, safety, and recommended dosage of weekly intravenous bolus 5-fluorouracil (5-FU) in children and young adults with recurrent ependymoma. METHODS:Patients 22 years of age or less with recurrent ependymoma were treated with bolus dosage 5-FU weekly for 4 weeks followed by a 2-week rest period, defining one cycle. Patients could continue on therapy for 16 cycles. The starting 5-FU dosage was 500 mg/m(2). Dose-limiting toxicity was determined after one cycle. Patients were initially enrolled according to a rolling-6 design; subsequent dose re-escalation phase was based on a 3 + 3 design. RESULTS:We treated patients at 400 (n = 6), 500 (n = 15), and 650 (n = 5) mg/m(2), with de-escalation due to toxicity. Twenty-three of twenty-six patients enrolled were evaluable. Five patients experienced grade 4 neutropenia (n = 2: 650 mg/m(2); n = 3: 500 mg/m(2)). One patient experienced grade 3 diarrhea. At 500 mg/m(2), the median 5-FU maximal concentration, AUC0-∞, and alpha half-life were 825 µM, 205 µM × h, and 9.9 min, respectively. Interim analysis revealed an association between hematologic toxicity and prior number of chemotherapeutic regimens (P = .03). The study was amended to re-escalate the dosage in a less heavily pretreated cohort of patients. CONCLUSIONS:These phase I clinical data provide initial pharmacokinetic parameters to describe i.v. bolus 5-FU disposition in children with recurrent ependymoma. Tumor exposures effective in preclinical testing can be achieved with tolerable bolus dosages in patients. Bolus 5-FU is well tolerated and possesses antitumor activity.
journal_name
Neuro Oncoljournal_title
Neuro-oncologyauthors
Wright KD,Daryani VM,Turner DC,Onar-Thomas A,Boulos N,Orr BA,Gilbertson RJ,Stewart CF,Gajjar Adoi
10.1093/neuonc/nov181subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1620-7issue
12eissn
1522-8517issn
1523-5866pii
nov181journal_volume
17pub_type
杂志文章相关文献
NEURO-ONCOLOGY文献大全abstract:Background:Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly diagnosed and posttreatment settings. Methods...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章
doi:10.1093/neuonc/noy022
更新日期:2018-08-02 00:00:00
abstract::A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk ...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nov082
更新日期:2015-11-01 00:00:00
abstract::An increase in the incidence of CNS tumors has been observed in many countries in the last decades. The reality of this trend has been much debated, as it has happened during a period when computer-assisted tomography and MRI have dramatically improved the detection of these tumors. The Gironde CNS Tumor Registry prov...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor120
更新日期:2011-12-01 00:00:00
abstract::Histone deacetylase inhibitors that increase histone acetylation on transformed cells are being investigated as unique anticancer drugs. The aim of this investigation was to evaluate an antiproliferative activity of the histone deacetylase inhibitors sodium butyrate (NaBT) and trichostatin A on 5 glioma cell lines, T9...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/4.2.95
更新日期:2002-04-01 00:00:00
abstract::Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/now016
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:Accumulation and infiltration of microglia/brain macrophages around and into glioma tissue promote tumor invasion and expansion. One tumor-promoting mechanism of microglia/brain macrophages is upregulation of membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation of extracellular ma...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou324
更新日期:2015-02-01 00:00:00
abstract::Carmustine is used in the treatment of glioblastomas as locally applied chemotherapy in the form of biodegradable wafers, which are lined on the walls of the resection cavity at the end of the resection, to increase local concentrations and decrease systemic toxicity. A total of 44 patients with glioblastoma with gros...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos003
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not327
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lu...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now037
更新日期:2016-04-01 00:00:00
abstract:Background:CNS tumors, including medulloblastoma and pediatric glioblastoma (pGBM) account for the majority of solid pediatric malignancies. There remains an unmet need to identify novel treatment approaches in poor prognosis and relapsed pediatric brain tumors, where therapeutic options are limited. Small-molecule B-c...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nox134
更新日期:2018-01-22 00:00:00
abstract::A 67-year-old man presented with a 7-month history of insidiously progressive chorea, ataxia, and vertigo. Neurologic examination revealed deficits referable to the basal nuclei, cerebellar vermis, and vestibular nuclei. Small-cell lung cancer was diagnosed by fine-needle biopsy of a parahilar mass. After chemotherapy...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/4.3.192
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:Diffuse midline glioma (DMG) is a pediatric malignancy with poor prognosis. Most children die less than one year after diagnosis. Recently, mutations in histone H3 have been identified and are believed to be oncogenic drivers. Targeting this epigenetic abnormality using histone deacetylase (HDAC) inhibitors ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noz215
更新日期:2020-04-15 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinico...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not125
更新日期:2013-12-01 00:00:00
abstract::Difficulties of drug delivery across the blood-brain barrier (BBB) and failure to eliminate cancer stem cells (CSCs) are believed to be the major causes of tumor recurrences in children with medulloblastoma (MB). Seneca Valley virus-001 (SVV-001) is a naturally occurring oncolytic picornavirus that can be systemically...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq148
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Chemokine signaling may contribute to progression of low-grade gliomas (LGGs) by altering tumor behavior or impacting the tumor microenvironment. In this study, we investigated the role of CX3C chemokine receptor 1 (CX3CR1) signaling in malignant transformation of LGGs. METHODS:Ninety patients with LGGs wer...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noaa075
更新日期:2020-10-14 00:00:00
abstract::Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treat...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/noy178
更新日期:2019-01-14 00:00:00
abstract:BACKGROUND:No more than half of patients with neurofibromatosis type 1 (NF1)-associated optic pathway gliomas (OPGs) develop vision loss. Prospectively identifying those who will require therapy remains challenging, because no reliable factors have yet been identified that predict future vision loss. To determine wheth...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not068
更新日期:2013-08-01 00:00:00
abstract::The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters. Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations were repeated ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nor091
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou083
更新日期:2014-11-01 00:00:00
abstract:Background:Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and tumor initiating cell maintenance. The rate-limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in gliobla...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy012
更新日期:2018-07-05 00:00:00
abstract::Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 e...
journal_title:Neuro-oncology
pub_type: 杂志文章,多中心研究
doi:10.1093/neuonc/nop065
更新日期:2010-05-01 00:00:00
abstract:Background:Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods:The relatio...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/now304
更新日期:2017-08-01 00:00:00
abstract::Microglia, which contribute substantially to the tumor mass of glioblastoma, have been shown to play an important role in glioma growth and invasion. While a large number of experimental studies on functional attributes of microglia in glioma provide evidence for their tumor-supporting roles, there also exist hints in...
journal_title:Neuro-oncology
pub_type: 杂志文章,评审
doi:10.1093/neuonc/nos116
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:Brain metastases are generally considered to be well demarcated from the surrounding brain parenchyma, although infiltrative growth patterns have been observed. We systemically investigated infiltration patterns and expression of adhesion molecules in a large and well-defined series of autopsy cases of brain...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/not112
更新日期:2013-12-01 00:00:00
abstract::In this article we report the results of a study of the relationship between response and progression in 375 patients with recurrent glioma enrolled in phase II chemotherapy trials. We reviewed the records of patients from 8 consecutive phase II trials, including 225 patients with recurrent glioblastoma multiforme and...
journal_title:Neuro-oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1093/neuonc/1.4.282
更新日期:1999-10-01 00:00:00
abstract:Background:Copy number alterations form prognostic molecular subtypes of glioblastoma with clear differences in median overall survival. In this study, we leverage molecular data from several glioblastoma cohorts to define the distribution of copy number subtypes across random cohorts as well as cohorts with selection ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noy108
更新日期:2018-09-03 00:00:00
abstract::The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectiv...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos260
更新日期:2013-01-01 00:00:00
abstract::Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents are under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the serum angiogenic profile of patients ...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/noq170
更新日期:2011-01-01 00:00:00
abstract::PDGFRA is a critical gene in glioma biology. Similar to EGFR, PDGFRA has been shown to be overexpressed, amplified, mutated, or truncated in gliomas, particularly glioblastomas. In addition, PDGFRA has been recently shown to be rearranged in glioblastoma. However, the frequency, cooccurrence, and clinical value of PDG...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nos217
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme. This study combined bevacizumab, a vascular endothelial growth factor inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, with standard radia...
journal_title:Neuro-oncology
pub_type: 杂志文章
doi:10.1093/neuonc/nou029
更新日期:2014-07-01 00:00:00