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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
journal contributionposted on 2023-07-19, 06:31 authored by Karen Xu, Karthik Ramesh, Vicki HuangVicki 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
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.
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Science & TechnologyLife Sciences & BiomedicineRadiology, Nuclear Medicine & Medical Imagingglioblastomahistone deacetylaseepigenetic drugradiation sensitizermagnetic resonance spectroscopyBRAIN SPECTROSCOPIC MRIADJUVANT TEMOZOLOMIDERADIATION-THERAPYRADIOTHERAPYSURVIVALCONCOMITANTSYSTEMHDACGlioblastomaHumansHydroxamic AcidsNeoplasm Recurrence, LocalPilot ProjectsSulfonamides32 Biomedical and Clinical Sciences3211 Oncology and CarcinogenesisRare DiseasesCancerNeurosciencesBrain CancerBrain DisordersClinical Research6.1 Pharmaceuticals6 Evaluation of treatments and therapeutic interventions