Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.
Abstract
BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant
glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including
27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1)
bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each
month. The primary end point was a 6-month progression-free survival, and secondary
end points included safety and overall survival. Vascular endothelial growth factor
(VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha)
were assessed semiquantitatively in archival tumours using immunohistochemistry and
were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month
progression-free survivals were 40.6% and 44.4%, the radiographic response rates were
22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension
predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and
low VEGF were associated with poorer progression-free survival (PFS) among those with
GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis
(12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade
1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism.
CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared
with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar
to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov:
NCT00612430).
Type
Journal articleSubject
Administration, OralAdult
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Biomarkers, Tumor
Brain Neoplasms
Etoposide
Female
Glioma
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Treatment Failure
Vascular Endothelial Growth Factor A
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https://hdl.handle.net/10161/16102Published Version (Please cite this version)
10.1038/sj.bjc.6605412Publication Info
(2009). Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent
malignant glioma: a phase II study. Br J Cancer, 101(12). pp. 1986-1994. 10.1038/sj.bjc.6605412. Retrieved from https://hdl.handle.net/10161/16102.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Darell Doty Bigner
E. L. and Lucille F. Jones Cancer Distinguished Research Professor, in the School
of Medicine
The Causes, Mechanisms of Transformation and Altered Growth Control and New Therapy
for Primary and Metastatic Tumors of the Central Nervous System (CNS). There are
over 16,000 deaths in the United States each year from primary brain tumors such as
malignant gliomas and medulloblastomas, and metastatic tumors to the CNS and its covering
from systemic tumors such as carcinoma of the lung, breast, colon, and melanoma. An
estimated 80,000 cases of primary brain tumors were expected to
Annick Desjardins
Professor of Neurosurgery
Allan Howard Friedman
Guy L. Odom Distinguished Professor of Neurosurgery, in the School of Medicine
At the present time, I am participating in collaborative research in the areas of
primary malignant brain tumors, epilepsy and subarachnoid hemorrhage. Primary malignant
brain tumors are increasing in frequency. Patients harboring glioblastoma, the most
malignant primary brain tumor, have a life expectancy of less than one year. In colloboration
with the Division of Neurology and the Department of Pathology, clinical and laboratory
trials have been initiated to identify better
Henry Seth Friedman
James B. Powell, Jr. Distinguished Professor of Pediatric Oncology, in the School
of Medicine
Overview: Our laboratory is pursuing a comprehensive analysis of the biology and
therapy of adult and childhood central nervous system malignancies, particularly high-grade
medulloblastoma, glioma, and ependymoma. Laboratory Studies: Active programs,
using human adult and pediatric CNS tumor continuous cell lines, transplantable xenografts
growing subcutaneously and intracranially in athymic nude mice and rats, and as well
as in the subarachnoid space of the ath
Sridharan Gururangan
Professor of Pediatrics
Dr. Gururangan is the Director of the Pediatric Neuro-Oncology program at the Preston
Robert Tisch Brain Tumor Center. His current research interest focuses on finding
novel chemotherapeutic strategies for the treatment of children and young adults with
central nervous system tumors. Since beginning his tenure at the Brain Tumor Center
at Duke, he has written seven clinical protocols. These protocols have incorporated
some of the important laboratory findings obtained from the laboratory of Dr.
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
James Emmett Herndon II
Professor of Biostatistics & Bioinformatics
Current research interests have application to the design and analysis of cancer clinical
trials. Specifically, interests include the use of time-dependent covariables within
survival models, the design of phase II cancer clinical trials which minimize some
of the logistical problems associated with their conduct, and the analysis of longitudinal
studies with informative censoring (in particular, quality of life studies of patients
with advanced cancer).
Roger Edwin McLendon
Professor of Pathology
Brain tumors are diagnosed in more than 20,000 Americans annually. The most malignant
neoplasm, glioblastoma, is also the most common. Similarly, brain tumors constitute
the most common solid neoplasm in children and include astrocytomas of the cerebellum,
brain stem and cerebrum as well as medulloblastomas of the cerebellum. My colleagues
and I have endeavored to translate the bench discoveries of genetic mutations and
aberrant protein expressions found in brain tumors to better understan
John Howard Sampson
Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine
Current research activities involve the immunotherapeutic targeting of a tumor-specific
mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific
epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches
using peptide vaccines and dendritic cells. Another area of interest involves drug
delivery to brain tumors. Translational and clinical work is carried out in this area
to formulate the relationship between various direct intratu
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