Veldhuijzen van Zanten SEM, El-Khouly FE, Jansen MHA, Bakker
DP, Sanchez Aliaga E, Haasbeek CJA, Wolf NI, Zwaan CM, Vandertop WP, van
Vuurden DG, Kaspers GJL. A phase I/II study of gemcitabine during radiotherapy
in children with newly diagnosed diffuse intrinsic pontine glioma. J Neurooncol.
2017 Jul 26. doi:10.1007/s11060-017-2575-9.
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.
____________________________________________________________________
A phase I/II, open–label, single–arm trial was carried out
with the goal to study 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). For this group of patients, gemcitabine up to
200 mg/m2/once weekly, added to radiotherapy, was found to be safe and well
tolerated.
Methods
The clinicians administered six doses of weekly gemcitabine
intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy.
Moreover, they gave increasing doses of 140, 175 and 200
mg/m2 gemcitabine to successive cohorts, following a 3+3 dose-escalation
schedule without expansion cohort.
Monitoring was done for dose-limiting toxicities (DLT)
during treatment period.
They used predefined case report forms to evaluate clinical
response.
Radiological response was assessed using the modified RANO
criteria.
PedsQL questionnaires were utilized to appraise quality of
life (QoL).
Results
This study incorporated nine patients, between June 2012 and
December 2016.
Treatment was found to be well tolerated.
This study did not find DLTs up to the maximum dose of 200
mg/m2.
Reduction of tumor-related symptoms were observed in all
patients.
Findings reported that QoL tended to improve during
treatment.
4.8 months (95% CI 4.0–5.7) and 8.7 months (95% CI 7.0–10.4)
were PFS and MOS.
By classifying patients according to the recently developed
DIPG survival prediction model, this study noticed a PFS and MOS of 6.4 and
12.4 months in intermediate risk patients (n=4), versus a PFS and MOS of 4.5
and 8.1 months, respectively, in high risk patient (n=5).
https://www.mdlinx.com/neurology/medical-news-article/2017/07/27/diffuse-intrinsic-pontine-glioma-dipg-radiotherapy/7263864/?category=latest&page_id=3
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