Hg-93concurrent Use of Panobinostat and Re-irradiation in Children With Progressive Dipg: Report of 2 Cases
Year: 2016
Type: article
Study design: Case Report
Abstract: Diffuse Intrinsic Pontine Glioma (DIPG) remains a devastating disease. Radiation therapy (RT) is the only modality which has been shown to improve the survival of patients with DIPG, however, it is not curative. Panobinostat is an oral histone deacetylase (HDAC) inhibitor which has been shown to have therapeutic efficacy both in vitro and in DIPG xenograft models. Preclinical studies have demonstrated radiosensitizing activity of this class of antitumor drugs, however, clinical data in DIPG is lacking. We recently treated two DIPG patients with Panobinostat after disease progression following initial treatment, including RT. Panobinostat was given at a dose of 20 mg and 15 mg (equivalent to 25 mg/m2 and 22 mg/m2), respectively, three times weekly for a duration of 4 months. Re-irradiation therapy (24 Gy) was also given. Significant improvement in symptoms was observed following the treatment, and both patients lived an additional 5 months following the initial progression. Except for a single episode of asymptomatic thrombocytopenia with rapid recovery in one patient, no drug-related adverse effects were observed. Panobinostat treatment resulted in increased acetylation of histone H4 and alpha-tubulin (a HDAC6 substrate) of peripheral blood mononuclear cells when examined by Western blots. In our experience, Panobinostat administered with re-irradiation was well tolerated at a relatively higher dose than that used in adult studies (20-30 mg/dose, equivalent to 11-17 mg/m2 using 1.8 m2 as average adult body surface area). Further investigation is warranted to confirm the efficacy and safety of combining Panobinostat with RT for DIPG potentially as frontline therapy.
Source: Neuro-Oncology
Authors: Zhihong Wang, Yubin Ge, Deniz Altinok, Janet Poulik, Sandeep Sood, Jeffrey Taub, Holly Pitman, Mark Kieran, Steven Miller
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2424420686