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1.
Beppu T Kamada K Nakamura R Oikawa H Takeda M Fukuda T Arai H Ogasawara K Ogawa A 《Journal of neuro-oncology》2003,61(2):161-170
Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68±14 days. The response rates (CR+PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors. 相似文献
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Prospective trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas. 总被引:4,自引:0,他引:4
Kazuhiko Ogawa Yoshihiko Yoshii Osamu Inoue Takafumi Toita Atsushi Saito Yasumasa Kakinohana Genki Adachi Yasunari Ishikawa Shigenari Kin Sadayuki Murayama 《Radiotherapy and oncology》2003,67(1):63-67
Twenty-one patients with high-grade gliomas were enrolled in a prospective trial of radiotherapy after hyperbaric oxygenation (HBO). Radiotherapy was administered in daily 2-Gy fractions up to a total dose of 60 Gy, and each fraction was delivered immediately after HBO. The current study indicated that radiotherapy immediately after HBO with chemotherapy was feasible for high-grade gliomas. 相似文献
4.
Teri N. Kreisl Svetlana Kotliarova John A. Butman Paul S. Albert Lyndon Kim Luna Musib Donald Thornton Howard A. Fine 《Neuro-oncology》2010,12(2):181-189
Enzastaurin, a potent inhibitor of protein kinase C-beta, inhibits angiogenesis and has direct cytotoxic activity against glioma cells in preclinical studies. Patients with recurrent high-grade gliomas were stratified by histology and use of enzyme-inducing antiepileptic drugs (EIAEDs). Patients on EIAED were treated on the phase I dose-escalation portion of the trial with evaluation of serum pharmacokinetics as the primary endpoint. Patients not on EIAED were treated on the phase II portion of the trial with radiographic response and progression-free survival (PFS) as primary objectives. Patients in phase I received enzastaurin 525–900 mg/d. Phase II patients received 500 or 525 mg/d. One hundred and eighteen patients were accrued to this trial. Therapy was well tolerated with thrombosis, thrombocytopenia, hemorrhage, and elevated alanine aminotransferase as the most commonly observed drug-associated grade 3 or higher toxicities. Patients on EIAED had serum enzastaurin exposure levels approximately 80% lower than those not on EIAED. Dose escalations up to 900 mg/d did not substantially increase serum exposure levels and a maximally tolerated dose was never reached. Twenty-one of 84 evaluable patients (25%) experienced an objective radiographic response. The 6-month PFS was 7% for patients with glioblastoma and 16% for patients with anaplastic glioma. Phosphorylation of glycogen synthase kinase-3 in peripheral blood mononuclear cells was identified as a potential biomarker of drug activity. Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy. 相似文献
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Seunggu J. Han John D. Rolston Annette M. Molinaro Jennifer L. Clarke Michael D. Prados Susan M. Chang Mitchel S. Berger Ashley DeSilva Nicholas A. Butowski 《Neuro-oncology》2014,16(9):1255-1262
Background
A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG).Methods
Sixty patients with recurrent HGG received temozolomide at 150 mg/m2/day on days 1–7 and days 15–21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes.Results
Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%–24%) with median OS of 21.6 weeks (95% CI, 16.9–30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%–73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29–8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9–27.3 weeks], log-rank test, P < .001).Conclusions
The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. (available at NCT00619112http://clinicaltrials.gov/ct2/show/). NCT00619112相似文献6.
Tomasz Trojanowski Jerzy P ceszyński Krzysztof Turowski Stanisław Kamiński Igor Gościński Marian Reinfus Tadeusz Krzyszkowski Marek Pyrich Adam Bielawski Czesława Leszczyk Barbara Bendarzewska Andrzej Staszczak Halina Koźniewska 《Journal of neuro-oncology》1988,6(3):285-291
A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6 000 rads after possibly radical removal of tumors. CCNU administration in the dosis of 100 mg/sq m of body surface every 6–8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61±7 weeks, while in those receiving additional chemotherapy was 56±4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality.
Address for offprints: T Trojanowski, Department of Neurosurgery, Medical School, Jaczewskiego 8, 20-950 Lublin, Poland 相似文献
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M Brada L Viviers C Abson F Hines J Britton S Ashley S Sardell D Traish A Gonsalves P Wilkins C Westbury 《Annals of oncology》2003,14(12):1715-1721
BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities. 相似文献
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Alexander M. Spence Mitchel S. Berger Robert B. Livingston Francis Ali-Osman Brian Griffin 《Journal of neuro-oncology》1992,12(2):187-191
Summary Twenty-one patients with recurrent malignant glioma who had failed prior chemotherapy with nitrosoureas were treated with high-dose intravenous cisplatin on days 1 and 8 of successive 4 week cycles. Fourteen patients were evaluable for response. Four patients showed partial responses; mean time to tumor progression (MTP) was 8 weeks. Six patients stabilized; MTP was 11 weeks. Four patients showed no response. There were no infectious or hemorrhagic complications, but partial hearing loss occurred in 7 patients and severe vomiting in 8 patients. High-dose intravenous cisplatin demonstrates substantial activity against malignant gliomas recurrent after chloroethylnitrosourea (CENU) failure. 相似文献
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《Expert review of anticancer therapy》2013,13(5):755-767
Malignant gliomas are one of the most difficult tumors to treat, with only modest advances being made in the past few decades. Surgery and radiation have had the greatest impact, increasing survival. Chemotherapy modestly increases survival. The use of chemotherapy in the treatment of malignant gliomas is the focus of this paper and the more commonly used agents at diagnosis and relapse are reviewed. Since most patients fail first-, second- and even third-line agents that are commercially available, some of the more relevant new biological compounds will also be discussed. As treatments for brain tumors evolve, it is likely that optimal therapies will come from combination therapies that incorporate target-specific and chemotherapeutic agents. 相似文献
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Antonio Omuro Timothy A. Chan Lauren E. Abrey Mustafa Khasraw Anne S. Reiner Thomas J. Kaley Lisa M. DeAngelis Andrew B. Lassman Craig P. Nolan Igor T. Gavrilovic Adilia Hormigo Cynthia Salvant Adriana Heguy Andrew Kaufman Jason T. Huse Katherine S. Panageas Andreas F. Hottinger Ingo Mellinghoff 《Neuro-oncology》2013,15(2):242-250
Background
In this phase II trial, we investigated the efficacy of a metronomic temozolomide schedule in the treatment of recurrent malignant gliomas (MGs).Methods
Eligible patients received daily temozolomide (50 mg/m2) continuously until progression. The primary endpoint was progression-free survival rate at 6 months in the glioblastoma cohort (N = 37). In an exploratory analysis, 10 additional recurrent grade III MG patients were enrolled. Correlative studies included evaluation of 76 frequent mutations in glioblastoma (iPLEX assay, Sequenom) aiming at establishing the frequency of potentially “drugable” mutations in patients entering recurrent MG clinical trials.Results
Among glioblastoma patients, median age was 56 y; median Karnofsky Performance Score (KPS) was 80; 62% of patients had been treated for ≥2 recurrences, including 49% of patients having failed bevacizumab. Treatment was well tolerated; clinical benefit (complete response + partial response + stable disease) was seen in 10 (36%) patients. Progression-free survival rate at 6 months was 19% and median overall survival was 7 months. Patients with previous bevacizumab exposure survived significantly less than bevacizumab-naive patients (median overall survival: 4.3 mo vs 13 mo; hazard ratio = 3.2; P = .001), but those patients had lower KPS (P = .04) and higher number of recurrences (P < .0001). Mutations were found in 13 of the 38 MGs tested, including mutations of EGFR (N = 10), IDH1 (N = 5), and ERBB2 (N = 1).Conclusions
In spite of a heavily pretreated population, including nearly half of patients having failed bevacizumab, the primary endpoint was met, suggesting that this regimen deserves further investigation. Results in bevacizumab-naive patients seemed particularly favorable, while results in bevacizumab-failing patients highlight the need to develop further treatment strategies for advanced MG.Clinical trials.gov identifier
(available at NCT00498927http://clinicaltrials.gov/ct2/show/) NCT00498927相似文献11.
Phase 1 dose escalation trial of the safety and pharmacokinetics of cabozantinib concurrent with temozolomide and radiotherapy or temozolomide after radiotherapy in newly diagnosed patients with high‐grade gliomas 下载免费PDF全文
David Schiff MD Annick Desjardins MD Timothy Cloughesy MD Thomas Mikkelsen MD Michael Glantz MD Marc C. Chamberlain MD David A. Reardon MD Patrick Y. Wen MD 《Cancer》2016,122(4):582-587
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Background To reduce this complication and to enhance the radiation effect to hypoxic cells of high-grade gliomas, the authors performed
noninvasive fractionated stereotactic radiotherapy (FSRT) using a Gamma unit combined with hyperbaric oxygen (HBO) therapy
for the treatment of recurrent disease.
Patients and methods Twenty-five consecutive patients who had previously received radiotherapy with chemotherapy for recurrent high-grade gliomas,
including 14 patients with anaplastic astrocytoma (AA) and 11 with glioblastoma multiforme (GBM), underwent Gamma FSRT immediately
after HBO therapy (2.5 atmospheres absolute for 60 min). The Gamma FSRT was repeatedly performed using a relocatable head
cast. Median tumor volume was 8.7 cc (range, 1.7–159.3 cc), and the median total radiation dose was 22 Gy (range, 18–27 Gy)
to the tumor margin in 8 fractions.
Results Actuarial median survival time after FSRT was 19 months for patients with AA and 11 months for patients with GBM, which was
significantly different (P = 0.012, log-rank test). Two patients underwent subsequent second FSRT for regional or remote recurrence. Seven patients
(28%) underwent subsequent craniotomies and resections at a mean of 8.4 months after FSRT treatment, and 4 of them had radiation
effects without viable cells and remained alive for 50–78 months.
Conclusion Gamma FSRT after HBO therapy appears to confer a survival benefit for patients with recurrent high-grade gliomas and warrants
further investigation. 相似文献
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Mee -Chou Kiu Chen -Nen Chang Wan -Chun Cheng Tzu -Kang Lin Cheuk -Wah Wong Simon G. Tang Wai -Man Leung Li -Hui Chen Yet -Sen Ho Kim -Thean Ng Jen -Shi Chen Tsai -Hsen Yang Gi -Ming Lai 《Journal of neuro-oncology》1995,25(3):215-220
Summary Twenty-two patients, aged 16 to 67, who had malignant gliomas after surgical resection were treated with carmustine and cisplatin intravenous infusion before, during, and after radiotherapy. All patients had subtotal or total resection, or biopsy as the initial procedure. Twenty-one patients who had at least 2 cycles of chemotherapy and finished the whole course of radiotherapy were considered to be evaluable for responses. Among them, 5 had glioblastoma multiforme, 16 had anaplastic astrocytoma. The median time to tumor progression was 35 weeks (range 12–130 weeks) and median survival time was 66 weeks (range 10–156 weeks). Early progression occurred more frequently in patients with biopsy only and subtotal resection, and in patients with glioblastoma than in those with anaplastic astrocytoma. This combined modality treatment program was associated with reversible hematologic toxicity which was severe in 2 patients, and with ototoxicity in 1 patient, nephrotoxicity in 2 patients. Combination of carmustine and cisplatin with cranial irradiation for malignant gliomas is moderately toxic and appears to offer no obvious survival advantage compared with radiation therapy plus BCNU alone. 相似文献
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Chemotherapy for high-grade gliomas 总被引:6,自引:0,他引:6
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Paul D Brown Caroline Chung Diane D Liu Sarah McAvoy David Grosshans Karine Al Feghali Anita Mahajan Jing Li Susan L McGovern Mary-Fran McAleer Amol J Ghia Erik P Sulman Marta Penas-Prado John F de Groot Amy B Heimberger Jihong Wang Terri S Armstrong Mark R Gilbert Nandita Guha-Thakurta Jeffrey S Wefel 《Neuro-oncology》2021,23(8):1337
BackgroundTo determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM).MethodsEligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs).ResultsA total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02).ConclusionsIn this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time. 相似文献
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Lone Gothard Phil Bryson Mark Glover Mary Woods Clare Peckitt Navita Somaiah Peter Mortimer 《Radiotherapy and oncology》2010,97(1):101-107
Background
A non-randomised phase II study suggested a therapeutic effect of hyperbaric oxygen (HBO) therapy on arm lymphoedema following adjuvant radiotherapy for early breast cancer, justifying further investigation in a randomised trial.Methods
Fifty-eight patients with ?15% increase in arm volume after supraclavicular ± axillary radiotherapy (axillary surgery in 52/58 patients) were randomised in a 2:1 ratio to HBO (n = 38) or to best standard care (n = 20). The HBO group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks. Primary endpoint was ipsilateral limb volume expressed as a percentage of contralateral limb volume. Secondary endpoints included fractional removal rate of radioisotopic tracer from the arm, extracellular water content, patient self-assessments and UK SF-36 Health Survey Questionnaire.Findings
Of 53/58 (91.4%) patients with baseline assessments, 46 had 12-month assessments (86.8%). Median volume of ipsilateral limb (relative to contralateral) at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. Twelve months after baseline the median (IQR) volume of the ipsilateral limb was 131.2% (IQR 122.7-151.5%) in the control group and 133.5% (IQR 122.3-144.9%) in the treatment group. Results for the secondary endpoints were similar between randomised groups.Interpretation
No evidence has been found of a beneficial effect of HBO in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer. 相似文献18.
尼妥珠单抗联合放疗加同期替莫唑胺治疗高分级胶质瘤的初步研究 总被引:1,自引:0,他引:1
背景与目的:尼妥珠单抗(nimotuzumab)是抗人表皮生长因子受体(epithelial growth factor receptor,EGFR)人源化单克隆抗体,能够抑制肿瘤细胞增殖并增加放化疗敏感性。本研究运用前瞻性方法对尼妥珠单抗联合放疗加同期替莫唑胺(temozolomide,TMZ)治疗高分级的脑胶质瘤(high-grade glioma,HGG)患者的不良反应和近期疗效进行初步观察。方法:2008年7月—2009年6月期间共17例HGG患者入组,均采用TMZ同期放化疗加TMZ辅助化疗,其中12例新诊断为HGG的患者放疗总剂量为60Gy/30次,3例复发HGG患者为50Gy/25次,2例脑干复发HGG患者为40Gy/20次;放疗期间每天口服TMZ50mg/m2,放疗结束后4周循环口服TMZ;放疗期间每周静脉滴注尼妥珠单抗注射液。记录治疗反应,计算6个月无疾病进展生存率和总生存率。结果:本组病例急性不良反应多为Ⅰ~Ⅱ级,没有Ⅲ级以上不良反应,有1例因发生Ⅱ级湿疹性皮炎,从而中断尼妥珠单抗治疗。16例作近期疗效评价,其中PR4例,SD10例,PD2例。6个月无进展生存率和总生存率分别为72.1%和86.3%。其中3例发生肿瘤假性进展。结论:本研究初步显示尼妥珠单抗联合放疗加同期替莫唑胺治疗HGG不良反应较小,患者可以耐受,近期疗效较好,远期疗效尚需进一步观察。 相似文献
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K Kohshi Y Kinoshita H Imada N Kunugita H Abe H Terashima N Tokui S Uemura 《British journal of cancer》1999,80(1-2):236-241
The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression. 相似文献
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Murray LJ Bridgewater CH Levy D 《Clinical oncology (Royal College of Radiologists (Great Britain))》2011,23(1):55-61