Bevacizumab and temozolomide in patients with first recurrence of WHO grade II and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled phase 2 EORTC trial

Bent, Martin J. van den; Klein, Martin; Smits, Marion; Reijneveld, Jaap C.; French, Pim J.; Clément, Paul M.; Vos, Filip Y.F. De; Wick, Antje; Mulholland, Paul J.; Taphoorn, Martin J.B.; Lewis, Joanne; Weller, Michael; Chinot, Olivier; Kros, Johan M.; Heer, Iris de; Verschuere, Tina; Coens, Corneel; Golfinopoulos, Vassilis; Gorlia, Thierry; Idbaïh, Ahmed

doi:10.1016/s1470-2045(18)30362-0

Cited by 90 publications

(59 citation statements)

References 24 publications

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“…The main chemotherapy used at relapse is temozolomide because of its good blood-brain barrier penetration and its favorable safety profile [ 119 , 120 ]. Bevacizumab, commonly used for recurrent high-grade astrocytomas, was evaluated in the “TAVAREC” randomized phase II trial in association with temozolomide, but no survival benefit was observed [ 121 ]. Regarding the other potential drugs for LGG at recurrence, the use of everolimus was associated with disease stability in a phase II trial [ 122 ], while the development of immunotherapies like vaccines [ 123 ] could open new opportunities for LGG patients.…”

Section: Role Of Chemotherapy and New Systemic Treatmentsmentioning

confidence: 99%

Clinical Management of Diffuse Low-Grade Gliomas

Lombardi

Barresi

Castellano

et al. 2020

Cancers

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Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care.

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Section: Role Of Chemotherapy and New Systemic Treatmentsmentioning

confidence: 99%

Clinical Management of Diffuse Low-Grade Gliomas

Lombardi

Barresi

Castellano

et al. 2020

Cancers

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“…Glioblastoma is the most common primary malignant brain tumor and continues to carry a very poor prognosis with a median survival of~20 months 1,2 Challenges in treating glioblastoma center around its molecular and cellular heterogeneity, including the presence of small populations of brain tumor initiating cells (BTICs) that are typically resistant to standard treatment regimens. 3,4 This complexity necessitates the development of therapies for targets that intersect multiple tumor-promoting pathways.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer effects of the HuR inhibitor, MS-444, in malignant glioma cells

Wang

Hjelmeland

Nabors

et al. 2019

Cancer Biology & Therapy

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Glioblastoma is a highly malignant and typically fatal tumor of the central nervous system. The tumor is characterized by marked cellular and molecular heterogeneity, including a subpopulation of brain tumor initiating cells (BTICs) that are highly resistant to radiation and chemotherapy. We previously reported that the RNA-binding protein HuR is: (1) overexpressed in glioblastoma, (2) necessary for tumor growth in vivo, and (3) a positive regulator of tumor-promoting genes in glioblastoma. These findings provide strong evidence that HuR might be a viable therapeutic target in glioblastoma. In this report, we investigated the effects of MS-444, a small molecule inhibitor of HuR, in xenograft-derived human glioblastoma cells and BTICs. We found that MS-444 treatment of glioblastoma cells resulted in loss of viability and induction of apoptosis, with evidence implicating death receptor 5. BTICs were particularly sensitive to MS-444. At sub-lethal doses, MS-444 attenuated invasion of glioblastoma cells and BTICs in a transwell model. At the molecular level, MS-444 treatment led to an attenuation of mRNAs in different tumor promoting pathways including angiogenesis, immune evasion and suppression of apoptosis. Although cytoplasmic HuR was reduced with MS-444 treatment, the attenuation of mRNAs could not be explained by RNA destabilization. In summary, this report provides proof of concept that small molecule inhibition of HuR could be a viable approach for treatment of glioblastoma.

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“…Baumert et al, in recently published randomized study results, have reported that they did not find any significant difference in outcome of the overall patient population treated with either radiotherapy alone or TMZ chemotherapy alone [12]. On the other hand, in the just published EORTC trial, randomized controlled research on phase 2 published in Lancet, van den Bent et al have found no evidence of improved overall survival with bevacizumab (Avastin) and TMZ combination treatment versus TMZ monotherapy in patients with first recurrence of WHO grades II and III glioma, without 1p/19q codeletion [13].…”

Section: Where We Are Nowmentioning

confidence: 99%

“…Achieving a gross total resection of the tumor without significant complication requires a thorough understanding of available surgical approaches [15,17,[30][31][32]. For majority of those patients, short-course radiotherapy with concurrent and adjuvant TMZ will bring a benefit, while gain from bevacizumab is limited [13]. There have been some ideas that certain antiepileptics also have a favorable effect on the outcome with glioma patients, but these studies have not given affirmative results [33].…”

Section: Is There Hopementioning

confidence: 99%