Concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Conclusive results of a randomized phase III trial by the EORTC

Stupp, Roger; Mason, W. P.; Bent, M. J. van den; Weller, Michael; Fisher, B.; Taphoorn, Martin J.B.; Brandes, A.A.; Cairncross, Gregory; Lacombe, Denis; Mirimanoff, R.O.

doi:10.1016/s0028-3770(05)83425-3

Cited by 34 publications

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“…may still relevantly modify the disease in patients with newly diagnosed glioblastoma when 124 combined with radiotherapy (11). Accordingly, mTOR inhibition has been considered an 125 option for patients with treatment-naïve glioblastomas that likely lack some of the 126 mechanisms of resistance acquired at recurrence.…”

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confidence: 99%

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082)

Wick

Gorlia²,

Bady

et al. 2016

Clinical Cancer Research

121

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PURPOSE: EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methlyguanine-DNA-methlytransferase (MGMT) promoter. PATIENTS AND METHODS: Patients (n=257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n=111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered >38 patients alive at 12 months in the per protocol population. A non-comparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Pre-specified post hoc analyses of markers reflecting target activation were performed. RESULTS: Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% 2)] in the temozolomide arm and 69.6% ] in the temsirolimus arm [HR=1.16, p=0.47]. In multivariable prognostic analyses of clinical and molecular factors phosphorylation of mTORSer2448 in tumor tissue (HR=0.13, 95% CI (0.04-0.47), p=0.002), detected in 37.6%, was associated with benefit from temsirolimus. CON-CLUSIONS: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 3, 2016; DOI: 10.1158/1078-0432.CCR-15-3153 EORTC 26082 Wick et al. Page 2 2/26/

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confidence: 99%

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082)

Wick

Gorlia²,

Bady

et al. 2016

Clinical Cancer Research

121

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“…The approved conventional treatment regimen of TMZ for recurrent gliomas is a daily dose of 150-200 mg/m 2 of body-surface area by infusion or by mouth for 5 days, repeated every 28 days (27). In our previous in vivo experimental study relying on the use of a mouse melanoma pseudometastatic lung model (24), we obtained the same efficacy in terms of median survival period when comparing TMZ administered through inhalation to TMZ administered intravenously (23).…”

Section: Resultsmentioning

confidence: 71%

Temozolomide-Based Dry Powder Formulations for Lung Tumor-Related Inhalation Treatment

et al. 2010

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Purpose Temozolomide dry powder formulations for inhalation, performed with no excipient or with a lipid or lactose coating, have been evaluated. MethodsThe particle size of raw Temozolomide in suspension was reduced by means of a high-pressure homogenizing technique and the solvent was evaporated by spray-drying to obtain a dry powder. Physicochemical properties (crystalline state, thermal properties, morphology, particle size and moisture and drug content) were determined by means of X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, laser light scattering, thermogravimetric analysis and high-performance liquid chromatography, respectively. Aerodynamic properties and release profiles were also evaluated using a multistage liquid impinger and a modified USP type 2 dissolution apparatus adapted to inhaler products, respectively. ResultsThe dry powder formulations for inhalation had a high temozolomide content that ranged from 70 % to 100%, remains the temozolomide crystalline state and had a low moisture content. Aerodynamic evaluations showed high fine particle fractions of up to 51% related to the metered dose. The dissolution profile revealed a similarly fast temozolomide release from the formulations. Conclusions

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“…Treatment in those under 65 was standardised by the landmark EORTC 26981 trial, showing a 2 month survival benefit and a doubling of 2 year survival rates with concurrent radiotherapy (RT) and temozolomide (TMZ) chemotherapy followed by 6 months of adjuvant TMZ. The age cut off for this trial was 70 and, in the group of trial patients over the age of 65, the benefit of adding chemotherapy to radiotherapy was not statistically significant [2]. There is concern that long course chemotherapy and radiotherapy may in fact be detrimental to elderly and frail patients.…”

Section: Introductionmentioning

confidence: 84%

Glioblastoma in the elderly — How do we choose who to treat?

Lorimer¹,

Saran

Chalmers

et al. 2016

Journal of Geriatric Oncology

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Glioblastoma (GBM) is the commonest primary malignant brain tumour among the adult population. Incidence peaks in the 7 th and 8 th decades of life and as our global population ages, rates are increasing. GBM is an almost universally fatal disease with life expectancy in the range of 3-5 months amongst the elderly.The assessment of elderly GBM patients prior to treatment decisions is poorly researched and unstandardized. In order to begin tackling this issue we performed a cross-sectional survey across all UK based consultant neuro oncologists to review their current practice in assessing elderly GBM patients.There were 56 respondents from a total of 93 recipients (60% response rate). All respondents confirmed that at least some patients aged 70 or over were referred to their clinics from the local multidisciplinary team meeting (MDT). Only 18% of consultants routinely performed a cognitive or frailty screening test at initial consultation. Of those who performed a screening test, the majority reported that the results of the test changed their treatment decision in approximately 50% of cases. Participants ranked performance status as the most important factor in determining treatment decisions.Considering the heterogeneity of this patient population, we argue that performance status is a crude measure of vulnerability within this cohort. Elderly GBM patients represent a unique clinical scenario because of the complexity of distinguishing neuro oncology related symptoms from general frailty. There is a need for specific geriatric assessment models tailored to the elderly neuro oncology population in order to facilitate treatment decisions.

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Concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Conclusive results of a randomized phase III trial by the EORTC

Cited by 34 publications

References 0 publications

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082)

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082)

Temozolomide-Based Dry Powder Formulations for Lung Tumor-Related Inhalation Treatment

Glioblastoma in the elderly — How do we choose who to treat?

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