Effectiveness of antiangiogenic drugs in glioblastoma patients: A systematic review and meta-analysis of randomized clinical trials

Lombardi, Giuseppe; Pambuku, Ardi; Bellu, Luisa; Farina, Miriam; Puppa, Alessandro Della; Denaro, Luca; Zagonel, Vittorina

doi:10.1016/j.critrevonc.2017.01.018

Cited by 79 publications

(54 citation statements)

References 48 publications

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“…Overall, these findings are in line with previous studies of BEV for newly diagnosed glioblastoma, in which improvements in PFS with the addition of BEV to RT and TMZ did not translate to an OS benefit . A recent meta‐analysis showed that BEV improved PFS, both alone and in combination with chemotherapy, and both as first‐line treatment or in recurrent glioblastoma, but no improvement in OS was observed . The median OS of 6.4 months for BEV‐treated patients in the current study was shorter than that reported in a previous phase II trial of BEV at first recurrence (9 months) ; however, in that study (the BRAIN study), patients had no prior exposure to BEV.…”

Section: Discussionsupporting

confidence: 88%

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma

Brandes¹,

Gil-Gil

Saran

et al. 2018

The Oncologist

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Background. We assessed the efficacy and safety of bevacizumab (BEV) through multiple lines in patients with recurrent glioblastoma who had progressed after first-line treatment with radiotherapy, temozolomide, and BEV. Patients and Methods. TAMIGA (NCT01860638) was a phase II, randomized, double-blind, placebo-controlled, multicenter trial in adult patients with glioblastoma. Following surgery, patients with newly diagnosed glioblastoma received first-line treatment consisting of radiotherapy plus

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Section: Discussionsupporting

confidence: 88%

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma

Brandes¹,

Gil-Gil

Saran

et al. 2018

The Oncologist

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“…Unfortunately, this success has had only limited impact on overall survival of cancer patients, and rarely resulted in durable responses. Bevacizumab (Avastin), an FDA approved anti-angiogenic drug (anti-VEGF), did not show significant improvement in overall survival [112][113][114]. Therefore, other anti-angiogenic agents and combinatorial strategies are being tested to target complex tumor microenvironment.…”

Section: Inhibition Of Tumor Angiogenesis Enhances Anti-tumor Potentimentioning

confidence: 99%

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Nguyen

Guz-Montgomery

Saha

2020

Cells

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Oncolytic viruses (OVs) are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce anti-tumor immunity. OV-induced tumor immunity can be enhanced through viral expression of anti-tumor cytokines such as interleukin 12 (IL-12). IL-12 is a potent anti-cancer agent that promotes T-helper 1 (Th1) differentiation, facilitates T-cell-mediated killing of cancer cells, and inhibits tumor angiogenesis. Despite success in preclinical models, systemic IL-12 therapy is associated with significant toxicity in humans. Therefore, to utilize the therapeutic potential of IL-12 in OV-based cancer therapy, 25 different IL-12 expressing OVs (OV-IL12s) have been genetically engineered for local IL-12 production and tested preclinically in various cancer models. Among OV-IL12s, oncolytic herpes simplex virus encoding IL-12 (OHSV-IL12) is the furthest along in the clinic. IL-12 expression locally in the tumors avoids systemic toxicity while inducing an efficient anti-tumor immunity and synergizes with anti-angiogenic drugs or immunomodulators without compromising safety. Despite the rapidly rising interest, there are no current reviews on OV-IL12s that exploit their potential efficacy and safety to translate into human subjects. In this article, we will discuss safety, tumor-specificity, and anti-tumor immune/anti-angiogenic effects of OHSV-IL12 as mono-and combination-therapies. In addition to OHSV-IL12 viruses, we will also review other IL-12-expressing OVs and their application in cancer therapy.

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“…Since then, additional efforts have been made with small molecule kinase inhibitors that target multiple receptors involved in angiogenesis in glioblastoma and other brain tumors such as PDGF-R, FGF-R, VEGF-R, etc. These molecules have been so far used in Phase I–III trials; however, all of them have also failed and they are actually inferior to Avastin [ 205 ].…”

Section: Conventional and New Interventions That Target The Endothmentioning

confidence: 99%

Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies

Peleli

Moustakas

Papapetropoulos

2020

IJMS

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Glioblastoma and other brain or CNS malignancies (like neuroblastoma and medulloblastoma) are difficult to treat and are characterized by excessive vascularization that favors further tumor growth. Since the mean overall survival of these types of diseases is low, the finding of new therapeutic approaches is imperative. In this review, we discuss the importance of the interaction between the endothelium and the tumor cells in brain and CNS malignancies. The different mechanisms of formation of new vessels that supply the tumor with nutrients are discussed. We also describe how the tumor cells (TC) alter the endothelial cell (EC) physiology in a way that favors tumorigenesis. In particular, mechanisms of EC–TC interaction are described such as (a) communication using secreted growth factors (i.e., VEGF, TGF-β), (b) intercellular communication through gap junctions (i.e., Cx43), and (c) indirect interaction via intermediate cell types (pericytes, astrocytes, neurons, and immune cells). At the signaling level, we outline the role of important mediators, like the gasotransmitter nitric oxide and different types of reactive oxygen species and the systems producing them. Finally, we briefly discuss the current antiangiogenic therapies used against brain and CNS tumors and the potential of new pharmacological interventions that target the EC–TC interaction.

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Effectiveness of antiangiogenic drugs in glioblastoma patients: A systematic review and meta-analysis of randomized clinical trials

Cited by 79 publications

References 48 publications

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma

A Randomized Phase II Trial (TAMIGA) Evaluating the Efficacy and Safety of Continuous Bevacizumab Through Multiple Lines of Treatment for Recurrent Glioblastoma

Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy

Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies

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