The role of irinotecan-bevacizumab as rescue regimen in children with low-grade gliomas: a retrospective nationwide study in 72 patients

J Neurooncol. 2022 Apr;157(2):355-364. doi: 10.1007/s11060-022-03970-4. Epub 2022 Mar 3.

Abstract

Introduction: At least half of children with low-grade glioma (LGG) treated with first line chemotherapy experience a relapse/progression and may therefore need a second-line chemotherapy. Irinotecan-bevacizumab has been recommended in this setting in France after encouraging results of pilot studies. We performed a retrospective analysis to define the efficacy, toxicity and predictors for response to the combination on a larger cohort.

Methods: We reviewed the files from children < 19 years of age with progressive or refractory LGG treated between 2009 and 2016 in 7 French centers with this combination.

Results: 72 patients (median age 7.8 years [range 1-19]) received a median of 16 courses (range 3-30). The median duration of treatment was 9 months (range 1.4-16.2). 96% of patients experienced at least disease stabilization. The 6-month and 2-year progression-free survivals (PFS) were 91.7% [IC 95% 85.5-98.3] and 38.2% [IC 95% 28.2-51.8] respectively. No progression occurred after treatment in 18 patients with a median follow-up of 35.6 months (range 7.6-75.9 months). Younger patients had a worse PFS (p = 0.005). Prior chemoresistance, NF1 status, duration of treatment, histopathology or radiologic response did not predict response. The most frequent toxicities related to bevacizumab included grades 1-2 proteinuria in 21, epistaxis in 10, fatigue in 12 and hypertension in 8 while gastro-intestinal toxicity was the most frequent side effect related to irinotecan.

Conclusions: Bevacizumab-irinotecan has the potential of disease control clinically and radiographically in children with recurrent LGG whatever their previous characteristics; in many cases however these responses are not sustained, especially in younger children.

Keywords: Bevacizumab; Children; Irinotecan; Low grade glioma.

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bevacizumab / adverse effects
  • Brain Neoplasms* / pathology
  • Camptothecin / adverse effects
  • Child
  • Child, Preschool
  • Glioma* / drug therapy
  • Glioma* / pathology
  • Humans
  • Infant
  • Irinotecan
  • Neoplasm Recurrence, Local / pathology
  • Retrospective Studies
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Irinotecan
  • Camptothecin