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Keywords:

  • bevacizumab;
  • brain tumor;
  • chemotherapy;
  • irinotecan;
  • low-grade glioma;
  • recurrent brain tumors

Abstract

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. Pediatr Blood Cancer 2009;52:791–795. © 2009 Wiley-Liss, Inc.