Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas

Wenyin Shi*, Joshua D. Palmer, Maria Werner-Wasik, David W. Andrews, James J. Evans, Jon Glass, Lyndon Kim, Voichita Bar-Ad, Kevin Judy, Christopher Farrell, Nicole Simone, Haisong Liu, Adam P. Dicker, Yaacov R. Lawrence

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Panobinostat is an oral HDAC inhibitor with radiosensitizing activity. We investigated the safety, tolerability and preliminary efficacy of panobinostat combined with fractionated stereotactic re-irradiation therapy (FSRT) for recurrent high grade gliomas. Patients with recurrent high grade gliomas were enrolled in a 3 + 3 dose escalation study to determine dose limiting toxicities (DLTs), maximum tolerated dose (MTD), safety, tolerability, and preliminary efficacy. FSRT was prescribed to 30–35 Gy delivered in 10 fractions. Panobinostat was administrated concurrently with radiotherapy. Of 12 evaluable patients, 8 had recurrent GBM, and 4 had recurrent anaplastic astrocytoma. There were three grade 3 or higher toxicities in each the 10 and 30 mg cohorts. In the 30 mg cohort, there was one DLT; grade 4 neutropenia. One patient developed late grade 3 radionecrosis. The median follow up was 18.8 months. The PFS6 was 67, 33, and 83 % for 10, 20, and 30 mg cohorts, respectively. The median OS was 7.8, 6.1 and 16.1 months for the 10, 20 and 30 mg cohorts, respectively. Panobinostat administrated with FSRT is well tolerated at 30 mg. A phase II trial is warranted to assess the efficacy of panobinostat plus FSRT for recurrent glioma.

Original languageEnglish
Pages (from-to)535-539
Number of pages5
JournalJournal of Neuro-Oncology
Volume127
Issue number3
DOIs
StatePublished - 1 May 2016
Externally publishedYes

Keywords

  • HDAC inhibitor
  • Panobinostat
  • Phase I trial
  • Radiotherapy
  • Recurrent high grade glioma

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