title: Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas.
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.
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA. Wenyin.shi@jefferson.edu.
authors.forename: Wenyin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Palmer
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Andrews
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Evans
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Glass
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Lyndon
authors.initials: L
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Voichita
authors.initials: V
authors.lastname: Bar-Ad
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Judy
authors.affiliation: Department of Neurosurgery, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Farrell
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Simone
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Haisong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA, 19107, USA.|Department of Radiation Oncology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Yaacov R
authors.initials: YR
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D000077767:Panobinostat; D011379:Prognosis; D016634:Radiosurgery; D000069475:Re-Irradiation; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat
keywords: HDAC inhibitor; Panobinostat; Phase I trial; Radiotherapy; Recurrent high grade glioma
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