Avastin and Malignant Gliomas

Book Series: Controversies in Neuro-Oncology

Volume 1

by

Thomas C. Chen, Marc Chamberlain

DOI: 10.2174/97816080513281100101
eISBN: 978-1-60805-132-8, 2010
ISBN: 978-1-60805-519-7
ISSN: 2210-5565 (Print)



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Indexed in: Chemical Abstracts

Neuro-oncology is an embryonic field of cancer research with a number of clinical trials in progress. However, the prognosis on neuro-...[view complete introduction]

Table of Contents

Foreword

- Pp. i

Victor A. Levin

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Preface

- Pp. ii-iiii (2)

Thomas Chen

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Contributors

- Pp. iv-vii (4)

Thomas C. Chen and Marc Chamberlain

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The Basic Science of Avastin (Bevacizumab) Therapy

- Pp. 1-6 (6)

Florence M. Hofman and Thomas C. Chen

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Avastin for Recurrent Malignant Gliomas

- Pp. 7-11 (5)

Annick Desjardins and James J. Vredenburgh

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Avastin and Malignant Gliomas: Is there a Role?

- Pp. 12-18 (7)

Teri N. Kreisl

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Bevacizumab with Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

- Pp. 19-23 (5)

Fabio M. Iwamoto and Philip H. Gutin

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Bevacizumab Failure in Patients with Recurrent Malignant Glioma

- Pp. 24-27 (4)

Andrew D. Norden

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An Update on the Role of Anti-Angiogenic Therapy for Newly Diagnosed Glioblastoma

- Pp. 28-32 (5)

David A. Reardon, Sith Sathornsumetee and James V. Vredenburgh

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Bevacizumab Plus Radiotherapy in Malignant Gliomas: Is there a Role?

- Pp. 33-39 (7)

Minesh Mehta, Disha Patel and Arnab Chakravarti

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Bevacizumab and Malignant Glioma: Is there a Role for Upfront Therapy?

- Pp. 40-45 (6)

Jing Wu and Mark R. Gilbert

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Bevacizumab Toxicity in Glioblastoma

- Pp. 46-50 (5)

Dawit Aregawi and David Schiff

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Is Bevacizumab Administration Safe When Combined with Therapeutic Anticoagulation in Patients with High-grade Glioma?

- Pp. 51-53 (3)

Lisa R. Rogers

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Bevacizumab in the Treatment of Glioblastoma: Is there an Optimal Dose or Schedule?

- Pp. 54-58 (5)

L. Kamsheh, P. Kumthekar and J. J. Raizer

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Assessing Radiographic Response in Glioblastoma Following Avastin Treatment

- Pp. 59-73 (15)

Whitney B. Pope

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The Radiographic Interpretation of Response to Avastin in Glioblastoma Multiforme

- Pp. 74-80 (7)

Nicholas Butowski and Susan Chang

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Imaging Responses of Bevacizumab

- Pp. 81-93 (13)

R. Thind, Y. S. Mohan and T. Mikkelsen

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Assessing Radiographic Response to Bevacizumab in Patients with GBM

- Pp. 94-99 (6)

John W. Henson and Bart Keogh

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Neurosurgical Implications of Bevacizumab Therapy of Malignant Gliomas

- Pp. 100-106 (7)

Manish K. Aghi and Mitchel S. Berger

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Neurosurgical Implications of Avastin

- Pp. 107-110 (4)

Gazanfar Rahmathulla and Michael A. Vogelbaum

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Novel Applications for Bevacizumab and other Angiogenic Inhibitors

- Pp. 111-116 (6)

Marc C. Chamberlain

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Role of Avastin for Treatment of Central Nervous System Radiation Necrosis

- Pp. 117-126 (10)

Jing Wu and Victor A. Levin

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Salvage Chemotherapy with Bevacizumab for Recurrent Anaplastic Glioma

- Pp. 127-132 (6)

Marc C. Chamberlain

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Bevacizumab for Recurrent Glioma - A Personal View

- Pp. 133-139 (7)

Roger Stupp

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Inhibitors of VEGF Signaling Pathways in Glioblastoma: Is the Evidence Sufficient for Widespread Use? A European Perspective

- Pp. 140-143 (4)

M. J. van den Bent

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Bevacizumab (Avastin®) and Malignant Glioma: Is there a Role? A European Perspective

- Pp. 144-146 (3)

Michael Weller

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The European Perspective Regarding Avastin and Malignant Gliomas

- Pp. 147-151 (5)

Wolfgang Wick, Michael Platten and Antje Wick

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Sunitinib for the Treatment of Central Nervous System Glioma

- Pp. 152-157 (6)

Neyns Bart

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Cilengitide: A Novel Integrin Antagonist, in Malignant Glioma

- Pp. 158-161 (4)

L. Burt Nabors

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Development of Sorafenib in Malignant Gliomas: Rationale and Early Clinical Experience

- Pp. 162-170 (9)

Rachel Grossman and Jaishri Blakeley

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Aflibercept (VEGF-Trap) in High-Grade Gliomas

- Pp. 171-175 (5)

Jan Drappatz, Andrew D. Norden and Patrick Y. Wen

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Cediranib in Glioblastoma

- Pp. 176-183 (8)

Elizabeth R. Gerstner, Jorg H. Dietrich, Daphne Wang and Tracy T. Batchelor

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Bevacizumab for Malignant Gliomas: Comparative Study with Other Malignancies

- Pp. 184-189 (6)

Helen Gu and Thomas C. Chen

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Author Index

- Pp. 190-191 (2)

Thomas C. Chen and Marc Chamberlain

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Index

- Pp. 192-195 (4)

Bentham Science Publishers

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Foreword

Controversies in Neuro-Oncology: Avastin and Malignant Gliomas, edited by Thomas Chen and Marc Chamberlain, is a timely book for the clinician treating patients with high-grade gliomas. The book will find a ready audience among today's physicians practicing neuro-oncology, medical oncology, and radiation oncology. Bevacizumab (avastin) was recently approved by the FDA for use in patients with glioblastoma. The book that follows is a collation of 25 chapters from North America and Europe that discuss current knowledge that forms the basis for bevacizumab action, experience using bevacizumab in the treatment of high-grade gliomas, its impact on neuroimaging studies, its use with radiation therapy, and its use to ameliorate radiation damage to the CNS. In addition and for comparison, there are 5 chapters that discuss other drugs that have, as one site of action, inhibition of VEGF receptor(s). The editor and authors should be congratulated for compiling an informative book that helps us to understand how best to use bevacizumab in neuro-oncology practice.

Victor A. Levin
The University of Texas
M. D. Anderson Cancer Center


Preface

This is the first issue of our new series entitled Controversies in Neuro-oncology. The goal of this series is to stimulate timely discussion in different areas of neuro-oncology where is still considerable debate on a specific topic, hopefully leading to new studies that will result in a better understanding of the problem.

Our first issue "Avastin and Maligant Gliomas" certainly illustrates this point. Avastin is now approved by the FDA as standalone therapy for patients with recurrent glioblastoma multiforme (GBM). It is the third FDA approved therapy for GBM, besides Gliadel (BCNU wafers) and temozolomide. However, the role, usage, and treatment endpoint of Avastin , still remains undefined in many instances. This issue highlights this point.

Hofman and Chen review the basic science and rationale for the use of Avastin as an anti-angiogenesis agent. The use of Avastin and CPT-11 (irinotecan) in the setting of recurrent GBM is highlighted in the Duke experience presented by Desjardins and Vredenburgh. Subsequently, the use of Avastin alone was demonstrated by Kreisl et al. to be similar to Avastin and CPT-11 in a National Cancer Institute (NCI) trial, leading to FDA approval of Avastin alone in the treatment of recurrent GBM, vs Avastin and CPT-11. Iwamoto and Gutin demonstrate that the addition of radiosurgery to previously radiatied patients does not increase radiation necrosis in the setting of Avastin. Norden presents the clinical and radiographic progression of recurrent glioma patients that have become resistant to Avastin, leading to rapid clinical progression and death.

The role of Avastin in upfront therapy is still to be defined. Reardon et al. present an update on the role of Avastin for newly diagnosed glioblastoma. Patel et al. discuss the effects of radiation therapy when combined with Avastin in the upfront setting. Wu and Gilbert discuss the upcoming Radiation Therapy Oncology Group (RTOG 0825) in which newly diagnosed patients are randomized to standard of care (radiation and temozolomide, followed by temozolomide alone) vs standard of care plus Avastin.

Kamsheh et al. discuss the various protocols to define the optimal dose and schedule for Avastin administration to minimize systemic toxicity. Avastin toxicity is discussed by Agregawi and Schiff. Rogers discusses her experience with anticoagulation for thromboembolism in patients receiving Avastin.

Defining the response to chemotherapy is currently based on the MacDonald criteria of changes in tumor size using contrast enhanced T1 MRI scans. However, Avastin actually decreases the "leakiness" of the blood tumor barrier, leading to decreased gadolinium enhancement of the GBM. As a result, standard methods of evaluation of tumor responses need to be clarified. Neuroradiographic evaluation of response to Avastin therapy is presented in a comprehensive chapter by Pope based on the UCLA experience with Avastin administration. Butowski and Chang present the problem with Avastin effects on the tumor vasculature, leading to mistaken interpretations on tumor response. Thind et al and Henson et al. present further insights into the imaging responses to Avastin, and response to therapy.

From the neurosurgical standpoint, Avastin therapy presents challenges from the standpoint of wound breakdown, and increased medical complications of thromboembolism, proteinuria, and hypertension. These considerations are well presented in chapters by Aghi and Berger, and by Rahmathulla and Vogelbaum.

Other potential novel applications of Avastin therapy are presented by Chamberlain in the use of Avastin for other cancers, including metastatic carcinoma and meningiomas. Wu and Levin present an unique chapter on the use of Avastin for radiation necrosis. Chamberlain reviews the use of Avastin for recurrent anaplastic gliomas.

Although the use of Avastin has been well received in the United States, its reception in Europe is much more guarded. European perspectives are presented by Stupp, van den Bent, Weller, and Wick et al. who advocate the use of further randomized trials for Avastin application in malignant gliomas.

Lastly, the use of other angiogenesis inhibitors that are currently in development is presented. Bart details the use of the tyrosine kinase inhibitor sunitinib for gliomas, and Nabors presents the use of the integrin inhibitor cilengitide for malignant gliomas. Grossman and Blakeley detail the development of another tyrosine kinase inhibitor sorafenib for treatment of malignant gliomas, and Drappatz et al. describe the use of the VEGF-trap Aflibercept in high grade gliomas. Lastly, Gerstner et al. outline the use of the VEGF receptor inhibitor cerdiranib for treatment of glioblastomas.

Finally, to put everything into perspective, Gu and Chen present a comparative study of how the use of Avastin is similar and different from Avastin therapy for other malignant cancers.

It is our hope that this ebook will highlight the nuances and complexities involved in Avastin therapy for malignant gliomas. Although Avastin therapy is still controversial in many ways, it has also become another pinnacle of hope for malignant glioma patients who otherwise would have no other therapy once they have progressed on temozolomide.

Thomas Chen
University of Southern California
USA

List of Contributors

Editor(s):
Thomas C. Chen
University of Southern
California
USA


Marc Chamberlain
University of Washington
USA




Contributor(s):
Manish K. Aghi
Department of Neurological Surgery
505 Parnassus Avenue, Rm M779
San Francisco, CA 94143-0112
USA


Dawit Aregawi
University of Michigan Hematology/Oncology
C369 Med Inn Building
1500 E Medical Center SPC 5848
Ann Arbor
MI, 48109-5848
USA


Neyns Bart
UZ Brussel
Laarbeeklaan 101
Brussel, 1090
Belgium


Tracy Batchelor
Stephen E. and Catherine Pappas Center for Neuro-Oncology
Yawkey 9E, Massachusetts General Hospital Cancer Center
55 Fruit Street
Boston
MA, 02114
USA


Mitchel S. Berger
Department of Neurological Surgery
505 Parnassus Avenue
Rm M779
San Francisco
CA, 94143-0112
USA


Jaishri Blakeley
Department of Neurology
The Johns Hopkins Oncology Center
600 North Wolfe Street
Baltimore
MD, 21287
USA


Nicholas Butowski
Department of Neuro-Oncology
Brain Tumor Research Center
University of California, San Francisco 400 Parnassus Avenue A808
San Francisco
California, 94143-0350
USA


Arnab Chakravarti
Ohio State University
Columbus
Ohio
USA


Marc C. Chamberlain
Fred Hutchinson Cancer Center, Seattle Cancer Care Alliance
825 Eastlake Ave E, POB 10923, MS: G4-940
Seattle
WA, 98109-1023
USA


Susan Chang
Department of Neuro-Oncology
Brain Tumor Research Center, University of California
San Francisco 400 Parnassus Avenue, A808
San Francisco
California, 94143-0350
USA


Thomas C. Chen
Departments of Neurosurgery
Keck School of Medicine
University of Southern California
Los Angeles
CA, 90033
USA


Annick Desjardins
Duke University Medical Center DUMC
Box 3624
Durham
NC, 27710
USA


Jörg H. Dietrich
Stephen E. and Catherine Pappas Center for Neuro-Oncology
Yawkey 9E, Massachusetts General Hospital Cancer Center
55 Fruit Street
Boston
MA, 02114
USA


Jan Drappatz
Center for Neuro-Oncology
Dana Farber Cancer Institute
44 Binney Street, SW-430D
Boston
MA, 02115
USA


Elizabeth R. Gerstner
Stephen E. and Catherine Pappas Center for Neuro-Oncology
Yawkey 9E, Massachusetts General Hospital Cancer Center
55 Fruit Street
Boston
MA, 02114
USA


Mark R. Gilbert
M. D. Anderson Cancer Center 1515 Holcombe Blvd.
Unit 431 Houston
Texas, 77030
USA


Rachel Grossman
Department of Neurosurgery
The Johns Hopkins Oncology Center
600 North Wolfe Street
Baltimore
MD, 21287
USA


Helen Gu
Norris Cancer Center
1441 Eastlake Ave.
Los Angeles
CA, 90033
USA


Philip H. Gutin
Department of Neurological Surgery
Weill Medical College of Cornell University
New York
USA


John W. Henson
Neurology
Swedish Neuroscience Institute
Suite 500, 550 17th Avenue
Seattle
WA, 98122
USA


Florence M. Hofman
Departments of Pathology
Keck School of Medicine
University of Southern
California
USA


Fabio M. Iwamoto
National Institute of Neurological Disorders and Stroke, National Institutes of Health
Bethesda
Maryland


L. Kamsheh
Northwestern University, Feinberg School of Medicine
Robert H. Lurie Comprehensive Cancer Center, 710 N. Lake Shore Drive
Abbott Hall, Room 1123
Chicago
IL, 60611
USA


Bart Keogh
Neuroradiology, Swedish Neuroscience Institute
550 17th Avenue, Suite 500
Seattle
WA, 98122
USA


Teri N. Kreisl
Neuro-Oncology Branch – NCI 9030
Old Georgetown Road, Bldg. 82, Rm. 243
Bethesda
MD, 20892
USA


Victor A. Levin
Department of Neuro-Oncology
The University of Texas, M. D. Anderson Cancer Center
Houston
TX, 77030
USA


Minesh Mehta
University of Wisconsin
Madison
WI
USA


T. Mikkelsen
Hermelin Brain Tumor Center, Depts. Neurology & Neurosurgery
E&R3096 Henry Ford Hospital 2799 West Grand Blvd
Detroit
MI, 48202
USA


Y.S. Mohan
Hermelin Brain Tumor Center, Depts. Neurology & Neurosurgery
E&R3096 Henry Ford Hospital 2799 West Grand Blvd
Detroit
MI, 48202
USA


L. Burt Nabors
Neuro oncology Program, University of Alabama at Birmingham
510 20th Street South, FOT 1020
Birmingham
AL, 35294
USA


Andrew D. Norden
Brigham and Women's Hospital , Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School
Boston
MA, 02115
USA


Disha Patel
Ohio State University
Columbus
Ohio
USA


Michael Platten
Department of Neurooncology
University Hospital of Heidelberg
Im Neuenheimer Feld 400, D-69120
Heidelberg
Germany


Whitney B. Pope
David Geffen School of Medicine, Department of Radiology
University of California
Los Angeles
USA


Gazanfar Rahmathulla
Brain Tumor and NeuroOncology Center
Cleveland Clinic, 9500 Euclid Ave
Cleveland
OH, 44195
USA


Jeffrey Raizer
Northwestern University, Feinberg School of Medicine
Robert H. Lurie Comprehensive Cancer Center
710 N. Lake Shore Drive, Abbott Hall, Room 1123
Chicago
IL, 60611
USA


David A. Reardon
Preston Robert Tisch Brain Tumor Center at Duke
Duke University Medical Center, Box 3624
Durham
NC, 27710
USA


Lisa R. Rogers
University Hospitals, Case Western Reserve Medical Center
11100 Euclid Avenue, Hanna House 517
Cleveland
Ohio, 44106
USA


Sith Sathornsumetee
Neuro-Oncology Program, Department of Medicine
Faculty of Medicine
Siriraj Hospital, Mahidol University
Bangkok
Thailand


David Schiff
University of Virginia, Health System
Box 800432
Charlottesville
VA, 22908-0432
USA


Roger Stupp
Department of Neurosurgery
University Hospital (CHUV)
Rue du Bugnon 46 CH-1011
Lausanne
Switzerland


R. Thind
Hermelin Brain Tumor Center, Depts. Neurology & Neurosurgery
E&R3096 Henry Ford Hospital 2799 West Grand Blvd
Detroit
MI , 48202
USA


M.J. Van den Bent
Dept Neuro-Oncology
Daniel den Hoed Cancer Center, Erasmus University Hospital
Rotterdam
The Netherlands


Michael A. Vogelbaum
Brain Tumor and Neuro-Oncology Center, Center for Translational Therapeutics, Department of Neurological Surgery
Cleveland Clinic / Neurological Institute
9500 Euclid Ave.
Cleveland
OH, 44195
USA


James V. Vredenburgh
Department of Medicine
The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
Durham
NC, 27710
USA


Daphne Wang
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Yawkey 9E, Massachusetts General Hospital Cancer Center
55 Fruit Street
Boston
MA, 02114
USA


Michael Weller
University Hospital Zurich
Switzerland


Patrick Y. Wen
Center for Neuro-Oncology, Dana Farber Cancer Institute
44 Binney Street, SW-430D
Boston
MA, 02115
USA


Antje Wick
Department of Neurooncology
University Hospital of Heidelberg
Im Neuenheimer Feld 400, D-69120
Heidelberg
Germany


Wolfgang Wick
Department of Neurooncology
University Hospital of Heidelberg
Im Neuenheimer Feld 400, D-69120
Heidelberg
Germany


Jing Wu
Dept of Neuro-Oncology
M. D. Anderson Cancer Center
1515 Holcombe Blvd., Unit 431
Houston
Texas, 77030
USA




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