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Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

dc.contributor.author Bigner, DD
dc.contributor.author Desjardins, A
dc.contributor.author Friedman, AH
dc.contributor.author Friedman, HS
dc.contributor.author Gururangan, Sridharan
dc.contributor.author Herndon, James Emmett II
dc.contributor.author Marcello, JE
dc.contributor.author McLendon, Roger E
dc.contributor.author Norfleet, J
dc.contributor.author Reardon, DA
dc.contributor.author Sampson, JH
dc.contributor.author Sathornsumetee, S
dc.contributor.author Vredenburgh, JJ
dc.coverage.spatial England
dc.date.accessioned 2018-03-01T14:21:08Z
dc.date.available 2018-03-01T14:21:08Z
dc.date.issued 2009-12-15
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/19920819
dc.identifier 6605412
dc.identifier.uri https://hdl.handle.net/10161/16102
dc.description.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).
dc.language eng
dc.relation.ispartof Br J Cancer
dc.relation.isversionof 10.1038/sj.bjc.6605412
dc.subject Administration, Oral
dc.subject Adult
dc.subject Aged
dc.subject Antibodies, Monoclonal
dc.subject Antibodies, Monoclonal, Humanized
dc.subject Antineoplastic Combined Chemotherapy Protocols
dc.subject Bevacizumab
dc.subject Biomarkers, Tumor
dc.subject Brain Neoplasms
dc.subject Etoposide
dc.subject Female
dc.subject Glioma
dc.subject Humans
dc.subject Male
dc.subject Middle Aged
dc.subject Neoplasm Recurrence, Local
dc.subject Treatment Failure
dc.subject Vascular Endothelial Growth Factor A
dc.title Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/19920819
pubs.begin-page 1986
pubs.end-page 1994
pubs.issue 12
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Faculty
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Neurology
pubs.organisational-group Neurology, General & Community Neurology
pubs.organisational-group Neurosurgery
pubs.organisational-group Orthopaedics
pubs.organisational-group Pathology
pubs.organisational-group Pediatrics
pubs.organisational-group Radiation Oncology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.publication-status Published
pubs.volume 101
dc.identifier.eissn 1532-1827


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