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

J Neurooncol. 2016 May;127(3):535-9. doi: 10.1007/s11060-016-2059-3. Epub 2016 Jan 29.

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.

Keywords: HDAC inhibitor; Panobinostat; Phase I trial; Radiotherapy; Recurrent high grade glioma.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Dose Fractionation, Radiation
  • Female
  • Follow-Up Studies
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Indoles / therapeutic use*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Panobinostat
  • Prognosis
  • Radiosurgery*
  • Re-Irradiation*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Hydroxamic Acids
  • Indoles
  • Panobinostat