Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan.
BACKGROUND
Chemotherapy has taken on a prominent role in the treatment of pediatric low-grade gliomas not amenable to gross total resections; however, there are few proven effective options for children with multiply recurrent tumors. Bevacizumab, a humanized immunoglobulin, monoclonal antibody that inhibits the activity of vascular endothelial growth factor and irinotecan have been used with some success in adults with malignant gliomas.


METHODS
Ten children with multiply recurrent low-grade gliomas were treated with the combination of bevacizumab and irinotecan. Patients received treatment at a median of 5.2 years of age, range 1.5-11.1 years. The majority had diencephalic tumors, three had neurofibromatosis type 1, and two had disseminated disease at the time of treatment. Nine of 10 patients had progressed after three or greater chemotherapy regimens and one also had received radiation therapy.


RESULTS
Seven patients had an objective neuroradiographic response, which was a complete response in one, partial response in three, and minor response in three. Clinical improvements were noted in seven, including improved visual acuity (2), improved motor function (2), weight gain in four with a diencephalic syndrome, and reversal of psychomotor retardation (3). Dose-limiting toxicities included transient leukoencephalopathy (1) and grade 3 protienuria (1). Response was durable in the majority of patients and six remain on treatment, for up to 22 months.


CONCLUSIONS
Multiply recurrent low-grade gliomas in children are responsive to the combination of bevacizumab and irinotecan. The drug combination has been relatively well tolerated, including in patients with neurofibromatosis type 1, and warrants further study.
Packer
Roger J
RJ
Division of Neurology, Children's National Medical Center, Washington, District of Columbia 20010, USA. rpacker@cnmc.org
Jakacki
Regina
R
Horn
Marianna
M
Rood
Brian
B
Vezina
Gilbert
G
MacDonald
Tobey
T
Fisher
Michael J
MJ
Cohen
Bruce
B
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*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D000077146:Irinotecan; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin