Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas.
OBJECTIVE
Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma.


METHODS
Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort (n=24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m(2) for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m(2) for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging.


RESULTS
The 6-month progression-free survival was 55% (95% confidence interval, 36-70%). The 6-month overall survival was 79% (95% confidence interval, 61-89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura.


CONCLUSIONS
Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma.
Desjardins
Annick
A
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. desja002@mc.duke.edu
Reardon
David A
DA
Herndon
James E
JE
Marcello
Jennifer
J
Quinn
Jennifer A
JA
Rich
Jeremy N
JN
Sathornsumetee
Sith
S
Gururangan
Sridharan
S
Sampson
John
J
Bailey
Leighann
L
Bigner
Darell D
DD
Friedman
Allan H
AH
Friedman
Henry S
HS
Vredenburgh
James J
JJ
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015331:Cohort Studies; D004264:DNA Topoisomerases, Type I / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016019:Survival Analysis
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin