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  • 1
    Online Resource
    Online Resource
    The Somatic Genomic Landscape of Glioblastoma
    Elsevier BV ; 2013
    In:  Cell Vol. 155, No. 2 ( 2013-10), p. 462-477
    Details
    In: Cell, Elsevier BV, Vol. 155, No. 2 ( 2013-10), p. 462-477
    Type of Medium: Online Resource
    ISSN: 0092-8674
    URL: Article
    DOI: 10.1016/j.cell.2013.09.034
    RVK:
    XA 36269
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 187009-9
    detail.hit.zdb_id: 2001951-8
    SSG: 12
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  • 2
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    Epidermal Growth Factor Receptor Variant III Status Defines Clinically Distinct Subtypes of Glioblastoma
    American Society of Clinical Oncology (ASCO) ; 2007
    In:  Journal of Clinical Oncology Vol. 25, No. 16 ( 2007-06-01), p. 2288-2294
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 16 ( 2007-06-01), p. 2288-2294
    Abstract: The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40–negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2006.08.0705
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2007
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Phase II Trial of the Antiangiogenic Agent Thalidomide in Patients With Recurrent High-Grade Gliomas
    American Society of Clinical Oncology (ASCO) ; 2000
    In:  Journal of Clinical Oncology Vol. 18, No. 4 ( 2000-02-14), p. 708-708
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 18, No. 4 ( 2000-02-14), p. 708-708
    Abstract: PURPOSE: Little progress has been made in the treatment of adult high-grade gliomas over the last two decades, thus necessitating a search for novel therapeutic strategies. Malignant gliomas are vascular or angiogenic tumors, which leads to the supposition that angiogenesis inhibition may represent a potentially promising strategy in the treatment of these tumors. We present the results of a phase II trial of thalidomide, a putative inhibitor of angiogenesis, in the treatment of adults with previously irradiated, recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of anaplastic mixed glioma, anaplastic astrocytoma, or glioblastoma multiforme who had radiographic demonstration of tumor progression after standard external-beam radiotherapy with or without chemotherapy were eligible. Patients were initially treated with thalidomide 800 mg/d with increases in dose by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved. Patients were evaluated every 8 weeks for response by both clinical and radiographic criteria. RESULTS: A total of 39 patients were accrued, with 36 patients being assessable for both toxicity and response. Thalidomide was well tolerated, with constipation and sedation being the major toxicities. One patient developed a grade 2 peripheral neuropathy after treatment with thalidomide for nearly a year. There were two objective radiographic partial responses (6%), two minor responses (6%), and 12 patients with stable disease (33%). Eight patients were alive more than 1 year after starting thalidomide, although almost all with tumor progression. Changes in serum levels of basic fibroblastic growth factor (bFGF) were correlated with time to tumor progression and overall survival. CONCLUSION: Thalidomide is a generally well-tolerated drug that may have antitumor activity in a minority of patients with recurrent high-grade gliomas. Future studies will better define the usefulness of thalidomide in newly diagnosed patients with malignant gliomas and in combination with radiotherapy and chemotherapy. Additionally, studies will be needed to confirm the potential utility of changes in serum bFGF as a marker of antiangiogenic activity and/or glioma growth.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2000.18.4.708
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2000
    detail.hit.zdb_id: 2005181-5
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  • 4
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    Phase II Trial of Tipifarnib in Patients With Recurrent Malignant Glioma Either Receiving or Not Receiving Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study
    American Society of Clinical Oncology (ASCO) ; 2006
    In:  Journal of Clinical Oncology Vol. 24, No. 22 ( 2006-08-01), p. 3651-3656
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 22 ( 2006-08-01), p. 3651-3656
    Abstract: A phase II study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG). Patients and Methods Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety. Results Two AG patients (9.1%) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% CI, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% CI, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving EIAEDs) seemed similar in EIAED and non-EIAED subgroups. Conclusion Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2006.06.2323
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2006
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Online Resource
    Cognitive Function as a Predictor of Survival in Patients With Recurrent Malignant Glioma
    American Society of Clinical Oncology (ASCO) ; 2000
    In:  Journal of Clinical Oncology Vol. 18, No. 3 ( 2000-02-01), p. 646-646
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 18, No. 3 ( 2000-02-01), p. 646-646
    Abstract: PURPOSE: To determine the contribution of cognitive function in predicting the survival of patients with recurrent malignant brain tumors. PATIENTS AND METHODS: A total of 80 patients with recurrent glioblastoma multiforme or anaplastic astrocytoma were seen for baseline evaluations before beginning a phase I or phase II clinical trial. Each patient received a battery of nine brief tests measuring cognitive function, ability to perform activities of daily living (ADLs), and quality of life (QOL). Tests were given monthly after treatment was begun. RESULTS: Performance on a test of verbal memory was independently and strongly related to survival after accounting for age, Karnofsky performance status score, histology, and time since diagnosis. Models incorporating three of nine and all nine tests in the battery accounted for significantly more variance in survival than did the clinical variables alone. Measures of QOL and ADLs (bathing, feeding, and so on) were not independently related to survival, although they provide clinical information that is important for patient care. CONCLUSION: These results indicate that a multifaceted assessment of cognition, QOL, and patient function is practical for brain tumor patients in clinical trials and can provide information regarding the relative risks versus benefits of new treatment regimens that supplements the information from the usual clinical variables.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2000.18.3.646
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2000
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    FoxM1 Promotes β-Catenin Nuclear Localization and Controls Wnt Target-Gene Expression and Glioma Tumorigenesis
    Elsevier BV ; 2011
    In:  Cancer Cell Vol. 20, No. 4 ( 2011-10), p. 427-442
    Details
    In: Cancer Cell, Elsevier BV, Vol. 20, No. 4 ( 2011-10), p. 427-442
    Type of Medium: Online Resource
    ISSN: 1535-6108
    URL: Article
    DOI: 10.1016/j.ccr.2011.08.016
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 2074034-7
    detail.hit.zdb_id: 2078448-X
    SSG: 12
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  • 7
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    Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 14 ( 2018-05-10), p. 1419-1427
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 14 ( 2018-05-10), p. 1419-1427
    Abstract: DNX-2401 (Delta-24-RGD; tasadenoturev) is a tumor-selective, replication-competent oncolytic adenovirus. Preclinical studies demonstrated antiglioma efficacy, but the effects and mechanisms of action have not been evaluated in patients. Methods A phase I, dose-escalation, biologic-end-point clinical trial of DNX-2401 was conducted in 37 patients with recurrent malignant glioma. Patients received a single intratumoral injection of DNX-2401 into biopsy-confirmed recurrent tumor to evaluate safety and response across eight dose levels (group A). To investigate the mechanism of action, a second group of patients (group B) underwent intratumoral injection through a permanently implanted catheter, followed 14 days later by en bloc resection to acquire post-treatment specimens. Results In group A (n = 25), 20% of patients survived 〉 3 years from treatment, and three patients had a ≥ 95% reduction in the enhancing tumor (12%), with all three of these dramatic responses resulting in 〉 3 years of progression-free survival from the time of treatment. Analyses of post-treatment surgical specimens (group B, n = 12) showed that DNX-2401 replicates and spreads within the tumor, documenting direct virus-induced oncolysis in patients. In addition to radiographic signs of inflammation, histopathologic examination of immune markers in post-treatment specimens showed tumor infiltration by CD8 + and T-bet + cells, and transmembrane immunoglobulin mucin-3 downregulation after treatment. Analyses of patient-derived cell lines for damage-associated molecular patterns revealed induction of immunogenic cell death in tumor cells after DNX-2401 administration. Conclusion Treatment with DNX-2401 resulted in dramatic responses with long-term survival in recurrent high-grade gliomas that are probably due to direct oncolytic effects of the virus followed by elicitation of an immune-mediated antiglioma response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.75.8219
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Online Resource
    Multicenter Phase II Trial of Temozolomide in Patients With Anaplastic Astrocytoma or Anaplastic Oligoastrocytoma at First Relapse
    American Society of Clinical Oncology (ASCO) ; 1999
    In:  Journal of Clinical Oncology Vol. 17, No. 9 ( 1999-09), p. 2762-2762
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 17, No. 9 ( 1999-09), p. 2762-2762
    Abstract: PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m 2 /d. Patients previously treated with chemotherapy received temozolomide 150 mg/m 2 /d; the dose could be increased to 200 mg/m 2 /d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR] ), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1999.17.9.2762
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1999
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Outcomes and Prognostic Factors in Recurrent Glioma Patients Enrolled Onto Phase II Clinical Trials
    American Society of Clinical Oncology (ASCO) ; 1999
    In:  Journal of Clinical Oncology Vol. 17, No. 8 ( 1999-08), p. 2572-2572
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 17, No. 8 ( 1999-08), p. 2572-2572
    Abstract: PURPOSE: To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. PATIENTS AND METHODS: Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. RESULTS: Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. CONCLUSION: Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1999.17.8.2572
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1999
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Phase II Trial of Temozolomide Plus the Matrix Metalloproteinase Inhibitor, Marimastat, in Recurrent and Progressive Glioblastoma Multiforme
    American Society of Clinical Oncology (ASCO) ; 2002
    In:  Journal of Clinical Oncology Vol. 20, No. 5 ( 2002-03-01), p. 1383-1388
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 20, No. 5 ( 2002-03-01), p. 1383-1388
    Abstract: PURPOSE: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. PATIENTS AND METHODS: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m 2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. RESULTS: Joint and tendon pain was the major therapy-related toxicity and was reported in 47% of patients. Five patients (11%) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39%. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16%. CONCLUSION: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29%. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2002.20.5.1383
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2002
    detail.hit.zdb_id: 2005181-5
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