Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment

Darmon, I.; Mc, Morisse; Blonski, Marie; Rhun, Émilie Le; Taillandier, Luc; Db, Roufai; Desenclos, C.; Trudel, Stéphanie; Jc, Faivre; Blanchard, Enka; Chauffert, Bruno; Boone, Mathieu

doi:10.7150/jca.18339

Cited by 8 publications

(3 citation statements)

References 15 publications

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“…Any form of combinatorial therapy was associated with better survival regardless of age. The highest survival benefit was seen in patients receiving chemotherapy, radiotherapy, and surgery as first‐line treatments, which is in keeping with the literature . This multi‐modality approach is usually attempted in children older than 3–5 years of age .…”

Section: Discussionsupporting

confidence: 79%

National cancer database analysis of outcomes in pediatric glioblastoma

et al. 2018

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Glioblastoma in children is an aggressive disease with no defined standard therapy. We evaluated hospital‐based demographic and survival patterns obtained through the National Cancer Database to better characterize children with glioblastoma. Our study identified 1173 patients from 0 to 19 years of age between 1998 and 2011. Comparisons were made among demographics, clinical characteristics, treatment, and survival variables. Fifty‐four percent of patients were over 10 years of age. Approximately 80% of patients underwent either partial or complete resection. Adjuvant therapy was used variably, and its use increased with patient age. Forty‐eight percent of patients received the combination of surgery, radiation, and chemotherapy, and 4% did not receive any treatment. As expected, patients ≤5 years of age had better 5‐year survival than those ages 6–10 (P = 0.01) or 11–19 years (P = 0.0077). Other factors associated with poor survival included black race and central tumor location. Better outcomes were associated with treatment that included surgery, radiotherapy, and chemotherapy compared to any other treatment combinations. Radiotherapy had no impact on survival in the 0 to 10‐year‐old age group, but was associated with improved survival for patients 11–19 years. We report an extensive demographic and survival analysis of pediatric glioblastoma. The observed differences likely reflect variances in tumor biology and likelihood of treatment receipt. Improved survival was associated with the use of surgery, radiotherapy, and chemotherapy. Radiation therapy was not associated with survival in patients younger than 10 years of age.

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Section: Discussionsupporting

confidence: 79%

National cancer database analysis of outcomes in pediatric glioblastoma

et al. 2018

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“…Defects in apoptotic mechanisms foster tumorigenesis and contribute to the resistance to temozolomide, since its cytotoxic activity is exerted in part through the triggering of apoptosis [8]. In recent years, new molecules have been developed to attempt to overcome the problem of tumor resistance to temozolomide, but with little impact on the prognosis and survival of GBM patients [9,10,11]. One strategy for improving GBM treatment is to seek new chemo-sensitizing agents that enhance the effectiveness of temozolomide by increasing the apoptosis of tumor cells through a decrease in the activity of the DNA repair enzyme.…”

Section: Introductionmentioning

confidence: 99%

Mifepristone Overcomes Tumor Resistance to Temozolomide Associated with DNA Damage Repair and Apoptosis in an Orthotopic Model of Glioblastoma

Llaguno-Munive

Romero-Piña

Serrano-Bello

et al. 2018

Cancers

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The standard treatment for glioblastoma multiforme (GBM) is surgery followed by chemo/radiotherapy. A major limitation on patient improvement is the high resistance of tumors to drug treatment, likely responsible for their subsequent recurrence and rapid progression. Therefore, alternatives to the standard therapy are necessary. The aim of the present study was to evaluate whether mifepristone, an antihormonal agent, has a synergistic effect with temozolomide (used in standard therapy for gliomas). Whereas the mechanism of temozolomide involves damage to tumor DNA leading to apoptosis, tumor resistance is associated with DNA damage repair through the O6-methylguanine-DNA-methyltransferase (MGMT) enzyme. Temozolomide/mifepristone treatment, herein examined in Wistar rats after orthotopically implanting C6 glioma cells, markedly reduced proliferation. This was evidenced by a decreased level of the following parameters: a proliferation marker (Ki-67), a tumor growth marker (18F-fluorothymidine uptake, determined by PET/CT images), and the MGMT enzyme. Increased apoptosis was detected by the relative expression of related proteins, (e.g. Bcl-2 (B-cell lymphoma 2), Bax (bcl-2-like protein 4) and caspase-3). Thus, greater apoptosis of tumor cells caused by their diminished capacity to repair DNA probably contributed significantly to the enhanced activity of temozolomide. The results suggest that mifepristone could possibly act as a chemo-sensitizing agent for temozolomide during chemotherapy for GBM.

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“…As second line treatment, Bevacizumab is commonly given, but is also less efficacious in these tumors compared to focal glioblastoma [42,43].…”

Section: Multifocal Glioblastomamentioning

confidence: 99%

Location of Glioblastoma and its Significance in Response to Treatment

Paldor

Sviri

2019

ANN

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Basal ganglia and thalamus glioblastomaDeep seated glioblastoma -tumors in the basal ganglia, insula and thalamus, have been shown to carry a worse prognosis as compared to glioblastoma in other locations [22,28,29]. However, extent of resection, a known predictor of outcome in glioblastoma, has also been shown to be significantly lower in deep seated glioblastomas [30][31][32][33]. It is unclear whether the worse prognosis is merely a representation of the lesser extent of resection or an actual survival difference. There has been no direct assessment of This work is licensed under Creative Commons Attribution 4.0 License ANN.MS.ID.000613.

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Temozolomide and Bevacizumab Induction before Chemoradiotherapy in Patients with Bulky Glioblastoma and/or with Severe Neurological Impairment

Cited by 8 publications

References 15 publications

National cancer database analysis of outcomes in pediatric glioblastoma

National cancer database analysis of outcomes in pediatric glioblastoma

Mifepristone Overcomes Tumor Resistance to Temozolomide Associated with DNA Damage Repair and Apoptosis in an Orthotopic Model of Glioblastoma

Location of Glioblastoma and its Significance in Response to Treatment

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