Bevacizumab and dose-intense temozolomide in recurrent high-grade glioma.
BACKGROUND
Angiogenesis inhibition is a rational treatment strategy for high-grade glioma (HGG). Combined antiangiogenic therapy and chemotherapy could be beneficial, taking advantage of different mechanisms of antitumour activity of both therapies. We carried out a phase I-II clinical trial with the combination of bevacizumab and continuous dose-intense temozolomide (TMZ) for patients with a recurrent HGG after first- or second-line treatment.


METHODS
Twenty-three HGG patients were treated with bevacizumab (10 mg/kg i.v. every 3 weeks) and TMZ (daily 50 mg/m(2)), until clinical or radiological progression. Conventional and dynamic magnetic resonance imaging (MRI) were carried out on days -4, 3 and 21 and until clinical or radiological progression.


RESULTS
Overall response rate (20%), 6-month progression-free survival (PFS6) (17.4%), median progression-free survival (13.9 weeks) and median overall survival (OS) (17.1 weeks) were considerably lower compared with most other studies with bevacizumab-containing regimens. The dynamic MRI parameters contrast transfer coefficient and relative cerebral blood volume decreased rapidly during the early phases of treatment, reflecting changes in vascularisation and vessel permeability but not in tumour activity. In addition, >50% of patients showed oedema reduction and a reduced shift on T1 images.


CONCLUSIONS
Treatment with bevacizumab and TMZ is feasible and well tolerated but did not improve PFS6 and median OS.
Verhoeff
J J C
JJC
Department of Radiation Oncology.
Lavini
C
C
Department of Radiology.
van Linde
M E
ME
Department of Medical Oncology.
Stalpers
L J A
LJA
Department of Radiation Oncology.
Majoie
C B L M
CBLM
Department of Radiology.
Reijneveld
J C
JC
Department of Neurology.
van Furth
W R
WR
Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Richel
D J
DJ
Department of Medical Oncology. Electronic address: d.j.richel@amc.uva.nl.
D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide