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Clinical Trial
. 2021 Jun;153(2):263-271.
doi: 10.1007/s11060-021-03763-1. Epub 2021 May 7.

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

Fatma E El-Khouly #  1   2 , Sophie E M Veldhuijzen van Zanten #  3   4   5 , Marc H A Jansen  3   6 , Dewi P Bakker  7 , Esther Sanchez Aliaga  8 , N Harry Hendrikse  8   9 , W Peter Vandertop  10 , Dannis G van Vuurden #  3   4 , Gertjan J L Kaspers #  3   4
Affiliations
Clinical Trial

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

Fatma E El-Khouly et al. J Neurooncol. 2021 Jun.

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.

Keywords: Bevacizumab; Diffuse intrinsic pontine glioma (DIPG); Erlotinib; Irinotecan; Targeted therapy.

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Conflict of interest statement

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Cumulative survival of DIPG patients: first progression (PFS)/start of the study (green dotted line), secondary progression/progression after study treatment (red line), and overall survival (blue line) for all study patients (a), intermediate-risk patients (b), and high-risk patients (c)
Fig. 2
Fig. 2
Disease course for every patient included in this study, from diagnosis until death. (PFS: progression free survival; OS: overall survival; RTx: radiotherapy; chemo: chemotherapy)
See this image and copyright information in PMC

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