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Clinical Trial
. 2017 Nov;135(2):307-315.
doi: 10.1007/s11060-017-2575-9. Epub 2017 Jul 26.

A phase I/II study of gemcitabine during radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma

Sophie E M Veldhuijzen van Zanten  1 , Fatma E El-Khouly  1   2 , Marc H A Jansen  1 , Dewi P Bakker  3 , Esther Sanchez Aliaga  4 , Cornelis J A Haasbeek  5 , Nicole I Wolf  3   6 , C Michel Zwaan  7 , W Peter Vandertop  8   9 , Dannis G van Vuurden  10   11 , Gertjan J L Kaspers  1   12
Affiliations
Clinical Trial

A phase I/II study of gemcitabine during radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma

Sophie E M Veldhuijzen van Zanten et al. J Neurooncol. 2017 Nov.

Erratum in

Abstract

The purpose of this phase I/II, open-label, single-arm trial is to investigate the safety, tolerability, maximum tolerated dose and preliminary efficacy of the potential radiosensitizer gemcitabine, administered concomitantly to radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Six doses of weekly gemcitabine were administered intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts received increasing doses of 140, 175 and 200 mg/m2 gemcitabine, respectively, following a 3 + 3 dose-escalation schedule without expansion cohort. Dose-limiting toxicities (DLT) were monitored during treatment period. Clinical response was assessed using predefined case report forms and radiological response was assessed using the modified RANO criteria. Quality of life (QoL) was assessed using PedsQL questionnaires. Between June 2012 and December 2016, nine patients were enrolled. Treatment was well tolerated, and no DLTs were observed up to the maximum dose of 200 mg/m2. All patients experienced reduction of tumor-related symptoms. QoL tended to improve during treatment. PFS and MOS were 4.8 months (95% CI 4.0-5.7) and 8.7 months (95% CI 7.0-10.4). Classifying patients according to the recently developed DIPG survival prediction model, intermediate risk patients (n = 4), showed a PFS and MOS of 6.4 and 12.4 months, respectively, versus a PFS and MOS of 4.5 and 8.1 months, respectively, in high risk patient (n = 5). Gemcitabine up to 200 mg/m2/once weekly, added to radiotherapy, is safe and well tolerated in children with newly diagnosed DIPG. PFS and MOS were not significantly different from literature.

Keywords: Diffuse intrinsic pontine glioma (DIPG); Gemcitabine; Radiosensitizer; Radiotherapy.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1
Fig. 1
Detailed disease course for each patient included in this study. The frame marks the treatment period of 6 weeks
See this image and copyright information in PMC

References

    1. Hargrave D, Bartels U, Bouffet E. Diffuse brainstem glioma in children: critical review of clinical trials. Lancet Oncol. 2006;7:241–248. doi: 10.1016/S1470-2045(06)70615-5. - DOI - PubMed
    1. Jansen MHA, van Vuurden DG, Vandertop WP, Kaspers GJL. Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev. 2012;38:27–35. doi: 10.1016/j.ctrv.2011.06.007. - DOI - PubMed
    1. Langmoen IA, Lundar T, Storm-Mathisen I, et al. Management of pediatric pontine gliomas. Childs Nerv Syst. 1991;7:13–15. doi: 10.1007/BF00263825. - DOI - PubMed
    1. Sigmond J, Honeywell RJ, Postma TJ et al (2008) Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer. doi:10.1093/annonc/mdn543 - PubMed
    1. Pauwels B, Korst AEC, Lardon F, Vermorken JB. Combined modality therapy of gemcitabine and radiation. Oncologist. 2005;10:34–51. doi: 10.1634/theoncologist.10-1-34. - DOI - PubMed

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