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
Karen Xu,
Karthik Ramesh,
Vicki Huang,
Saumya S. Gurbani,
James Scott Cordova,
Eduard Schreibmann,
Brent D. Weinberg,
Soma Sengupta,
Alfredo D. Voloschin,
Matthias Holdhoff,
Peter B. Barker,
Lawrence R. Kleinberg,
Jeffrey J. Olson,
Hui-Kuo G. Shu,
Hyunsuk Shim
Affiliations
Karen Xu
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Karthik Ramesh
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Vicki Huang
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Saumya S. Gurbani
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
James Scott Cordova
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Eduard Schreibmann
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Brent D. Weinberg
Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA
Soma Sengupta
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA
Alfredo D. Voloschin
Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA
Matthias Holdhoff
Department of Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
Peter B. Barker
Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD 21205, USA
Lawrence R. Kleinberg
Department of Radiation Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
Jeffrey J. Olson
Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
Hui-Kuo G. Shu
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
Hyunsuk Shim
Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA
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.
