UZH-Logo

Is there a world beyond bevacizumab in targeting angiogenesis in glioblastoma?


Seystahl, K; Weller, M (2012). Is there a world beyond bevacizumab in targeting angiogenesis in glioblastoma? Expert Opinion on Investigational Drugs, 21(5):605-617.

Abstract

INTRODUCTION: Antiangiogenic approaches are currently the dominating experimental therapeutic strategy in glioblastoma. First enthusiasm was provoked by promising radiological response rates and an apparent clinical benefit with some of these agents. Major limitations include the modest number of durable responses, the lack of cytotoxic antitumor activity, of synergy when combined with chemotherapy and of an overall survival benefit. AREAS COVERED: We review the rationale as well as preclinical and clinical evidence for the future development of antiangiogenic agents in glioblastoma. The most prominent approach targets VEGF and includes agents such as the VEGF antibody bevacizumab, the VEGF receptor fusion protein aflibercept or the tyrosine kinase inhibitors cediranib and XL-184. Inhibition of angiogenic pathways by small molecules, for example, enzastaurin, or anti-integrin-based approaches, for example, cilengitide, represent alternative strategies. EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II. By contrast, bevacizumab was conditionally approved in many countries. Recently completed Phase III trials for bevacizumab and cilengitide in the first-line setting will define the future role of these agents. This intense clinical trial activity reflects the hope that antiangiogenic agents will become part of the limited therapeutic options for glioblastoma.

INTRODUCTION: Antiangiogenic approaches are currently the dominating experimental therapeutic strategy in glioblastoma. First enthusiasm was provoked by promising radiological response rates and an apparent clinical benefit with some of these agents. Major limitations include the modest number of durable responses, the lack of cytotoxic antitumor activity, of synergy when combined with chemotherapy and of an overall survival benefit. AREAS COVERED: We review the rationale as well as preclinical and clinical evidence for the future development of antiangiogenic agents in glioblastoma. The most prominent approach targets VEGF and includes agents such as the VEGF antibody bevacizumab, the VEGF receptor fusion protein aflibercept or the tyrosine kinase inhibitors cediranib and XL-184. Inhibition of angiogenic pathways by small molecules, for example, enzastaurin, or anti-integrin-based approaches, for example, cilengitide, represent alternative strategies. EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II. By contrast, bevacizumab was conditionally approved in many countries. Recently completed Phase III trials for bevacizumab and cilengitide in the first-line setting will define the future role of these agents. This intense clinical trial activity reflects the hope that antiangiogenic agents will become part of the limited therapeutic options for glioblastoma.

Citations

11 citations in Web of Science®
17 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

17 downloads since deposited on 19 Sep 2012
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:19 Sep 2012 07:32
Last Modified:05 Apr 2016 15:57
Publisher:Informa Healthcare
ISSN:1354-3784
Publisher DOI:10.1517/13543784.2012.670219
PubMed ID:22413865
Permanent URL: http://doi.org/10.5167/uzh-64672

Download

[img]
Content: Published Version
Filetype: PDF - Registered users only
Size: 399kB
View at publisher
[img]
Preview
Content: Accepted Version
Filetype: PDF
Size: 303kB

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations