A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma

Fatma E El-Khouly, Sophie E M Veldhuijzen van Zanten, Marc H A Jansen, Dewi P Bakker, Esther Sanchez Aliaga, N Harry Hendrikse, W Peter Vandertop, Dannis van Vuurden, Gertjan J L Kaspers

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG).

METHODS: Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m2) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m2) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed.

RESULTS: Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5-10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m2. Median sPFS was 3.2 months (range 1.0-10.9), and median OS was 13.8 months (range 9.3-33.0). Overall QoL was stable during treatment.

CONCLUSIONS: Daily erlotinib is safe and well tolerated in doses up to 85 mg/m2 when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalJournal of Neuro-Oncology
Volume153
Issue number2
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Astrocytoma
  • Bevacizumab
  • Brain Stem Neoplasms/drug therapy
  • Child
  • Diffuse Intrinsic Pontine Glioma/drug therapy
  • Disease Progression
  • Erlotinib Hydrochloride
  • Humans
  • Irinotecan
  • Quality of Life

Fingerprint

Dive into the research topics of 'A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma'. Together they form a unique fingerprint.

Cite this