Final Report on Clinical Outcomes and Tumor Recurrence Patterns of a Pilot Study Assessing Efficacy of Belinostat (PXD-101) with Chemoradiation for Newly Diagnosed Glioblastoma

Tomography

Soma Sengupta¹  Alfredo D. Voloschin¹  Matthias Holdhoff²  Vicki Huang³  James Scott Cordova³  Karen Xu³  Karthik Ramesh³  Eduard Schreibmann³  Hyunsuk Shim³  Saumya S. Gurbani³  Hui-Kuo G. Shu³  Lawrence R. Kleinberg⁴  Brent D. Weinberg⁵  Peter B. Barker⁶  Jeffrey J. Olson⁷ 

[1] Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA;Department of Oncology, Johns Hopkins University, Baltimore, MD 21218, USA;Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA;Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD 21218, USA;Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA;Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21205, USA;Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA;

关键词: glioblastoma;    histone deacetylase;    epigenetic drug;    radiation sensitizer;    magnetic resonance spectroscopy;   

DOI  :  10.3390/tomography8020057

来源: DOAJ

【 摘 要 】

Glioblastoma (GBM) is highly aggressive and has a poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability, anti-GBM activity, and the potential to enhance chemoradiation. The purpose of this clinical trial was to assess the efficacy of combining belinostat with standard-of-care therapy. Thirteen patients were enrolled in each of control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500–750 mg/m² 1×/day × 5 days) every three weeks (weeks 0, 3, and 6 of RT). All patients received temozolomide and radiation therapy (RT). RT margins of 5–10 mm were added to generate clinical tumor volumes and 3 mm added to create planning target volumes. Median overall survival (OS) was 15.8 months for the control cohort and 18.5 months for the belinostat cohort (p = 0.53). The recurrence volumes (rGTVs) for the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients who experienced out-of-field recurrence, tumors were detectable by spectroscopic MRI before RT. Recurrence analysis suggests better in-field control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM. It may be particularly beneficial to combine this radio-sensitizing effect with spectroscopic MRI-guided RT.

【 授权许可】

Unknown