Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients

Behm, Timo; Horowski, Antonia; Schneider, Simon; Bock, Hans; Mielke, Dorothee; Rohde, Veit; Stockhammer, Florian

doi:10.1016/j.clineuro.2013.08.002

Cited by 30 publications

(15 citation statements)

References 23 publications

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“…The 2014 EANO guidelines reflected this concern by including the multimodality treatment as an option for fit elderly patients (9). A retrospective analysis of 293 patients over the age of 65 showed a benefit for the combined regimen (222). A retrospective survey of the National Cancer Database yielded similar results, with combined modality treatment showing superiority over both chemotherapy alone and RT alone, in a group of 16,717 patients, with nGBM, aged 65 years or older (223).…”

Section: Chemotherapy and Radiotherapysupporting

confidence: 51%

Current Standards of Care in Glioblastoma Therapy

et al. 2017

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Regardless of ideal multidisciplinary treatment, including maximal surgical resection, followed by radiotherapy plus concomitant and maintenance temozolomide (TMZ), almost all patients experience tumor progression with nearly universal mortality and a median survival of less than 15 months. The addition of bevacizumab to standard treatment with TMZ revealed no increase in overall survival (OS) but improved progression-free survival (PFS). In newly diagnosed GBM, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been shown to predict response to alkylating agents, as well asgnosis. Therefore, MGMT promoter status may have a crucial role in the choice of single modality treatment in fragile elderly population. No standard of care is established in recurrent or progressive GBM. Treatment alternatives may include supportive care, surgery, re-irradiation, systemic therapies, and combined modality therapy. Despite numerous clinical trials, the identification of effective therapies is complex because of the lack of appropriate control arms, selection bias, small sample sizes, and disease heterogeneity. Tumor-treating fields plus TMZ represent a major advance in the field of GBM therapy, and should be Standards of Care in Glioblastoma Therapy 198 considered for patients with newly diagnosed GBM with no contraindications. As a disease with such a poor prognosis, treatment of GBM should go beyond improving survival and aim at preserving and even improving the quality of life of both the patient and the caregiver.

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Section: Chemotherapy and Radiotherapysupporting

confidence: 51%

Current Standards of Care in Glioblastoma Therapy

et al. 2017

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“…The multi-target strategy has been assuming great importance in the therapy of GBM, a tumor for which the available treatments just offer a limited improvement in survival456. In terms of current multitherapy strategies, dual PI3K/mTOR inhibitors are emerging in GBM34.…”

Section: Discussionmentioning

confidence: 99%

“…Despite massive research efforts, the surgical resection and the currently approved anti-GBM agents, such as Temozolamide, and Bevacizumab, or Cilengitide, which is in clinical trials (http://clinicaltrials.gov), offer a limited improvement in progression free survival456. Escape from cell death is a hallmark of cancers and a major cause of treatment failure; in this respect, apoptosis inducers that act through the mitochondria death pathway have been emerging as promising drugs in a large number of tumors7, particularly in GBM8.…”

mentioning

confidence: 99%

Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

Daniele

Taliani

Pozzo

et al. 2014

Sci Rep

139

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In the complex scenario of cancer, treatment with compounds targeting multiple cell pathways has been emerging. In Glioblastoma Multiforme (GBM), p53 and Translocator Protein (TSPO), both acting as apoptosis inducers, represent two attractive intracellular targets. On this basis, novel indolylglyoxylyldipeptides, rationally designed to activate TSPO and p53, were synthesized and biologically characterized. The new compounds were able to bind TSPO and to reactivate p53 functionality, through the dissociation from its physiological inhibitor, murine double minute 2 (MDM2). In GBM cells, the new molecules caused Δψm dissipation and inhibition of cell viability. These effects resulted significantly higher with respect to those elicited by the single target reference standards applied alone, and coherent with the synergism resulting from the simultaneous activation of TSPO and p53. Taken together, these results suggest that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM.

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“…Patients were informed of the investigational nature of this study and written informed consent was obtained from each patient in accordance with insti tutional guidelines. Patients with a Karnofsky Per formance Scale (KPS) score ≥ 70 and age < 60 were included to receive conventional radiotherapy and chemotherapy after surgical resection: 1.82.0 Gy per day, over a period of 6 weeks, for a total dose of 60 Gy and temozolomide therapy at a dose of 75 mg/m 2 per day, seven days a week for 42 con secutive days during radiotherapy (as used in the EORTC study by Stupp et al) [3,23,36].…”

Section: Methodsmentioning

confidence: 99%

Original article Prognostic significance of the markers IDH1 and YKL40 related to the subventricular zone

Batista¹,

Vega²,

Eulate-Beramendi³

et al. 2015

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Glioblastoma multiforme (GBM), a highly aggressive brain cancer characterized by uncontrolled proliferation, resistance to cell death, angiogenesis, and vascular edema, remains one of the deadliest types of cancer. The subventricular zone (SVZ) harbors cells with great proliferative potential, and the microenvironment within the SVZ is permissive to growth and proliferation. This neurogenic niche is suspected to be a vulnerable site for the origin of subtypes of GBM. The aim of our study was to determine the immunohistochemical expression of mIDH1 and YKL40 in relationship to the SVZ of GBMs. YKL40, also known as chitinase-like protein 1, is included as a mesenchymal marker and associated with a poor prognosis. The protein is a secreted inflammatory molecule with no chitinolytic activity. However, the mutation of IDH1 (mIDH1) has been found in the cytoplasm and peroxisomes of 70-80% of secondary GBMs. In our study we found that YKL40-positive GBM is significantly linked to SVZ types IV and V (p < 0.0001). Our results show the diversity among GBMs related to the SVZ, which should be considered in the design of future targeted therapies. There was a significant impact of patient age, mIDH1 positivity, SVZ type III, and chemoradiotherapy on overall survival.

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Concomitant and adjuvant temozolomide of newly diagnosed glioblastoma in elderly patients

Cited by 30 publications

References 23 publications

Current Standards of Care in Glioblastoma Therapy

Current Standards of Care in Glioblastoma Therapy

Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

Original article Prognostic significance of the markers IDH1 and YKL40 related to the subventricular zone

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