1. 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
- Author
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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, and Hyunsuk Shim
- Subjects
glioblastoma ,histone deacetylase ,epigenetic drug ,radiation sensitizer ,magnetic resonance spectroscopy ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
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.
- Published
- 2022
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