A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma.
OBJECTIVE
The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM.


METHODS
From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involved-field radiation therapy and concomitant temozolomide (75 mg/m(2) daily for 42 days) along with bevacizumab (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m(2) on Days 1-7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle.


RESULTS
The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients.


CONCLUSIONS
The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.
Departments of Radiation Oncology, New York University Langone Medical Center, New York, New York 10016, USA. ashwatha.narayana@nyumc.org
Ashwatha
A
Narayana
Deborah
D
Gruber
Saroj
S
Kunnakkat
John G
JG
Golfinos
Erik
E
Parker
Shahzad
S
Raza
David
D
Zagzag
Patricia
P
Eagan
Michael L
ML
Gruber
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011379:Prognosis; D012008:Recurrence; D000077204:Temozolomide; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide