TY - JOUR
T1 - Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas
AU - Shi, Wenyin
AU - Palmer, Joshua D.
AU - Werner-Wasik, Maria
AU - Andrews, David W.
AU - Evans, James J.
AU - Glass, Jon
AU - Kim, Lyndon
AU - Bar-Ad, Voichita
AU - Judy, Kevin
AU - Farrell, Christopher
AU - Simone, Nicole
AU - Liu, Haisong
AU - Dicker, Adam P.
AU - Lawrence, Yaacov R.
N1 - Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - HDAC inhibitor
KW - Panobinostat
KW - Phase I trial
KW - Radiotherapy
KW - Recurrent high grade glioma
UR - http://www.scopus.com/inward/record.url?scp=84955577526&partnerID=8YFLogxK
U2 - 10.1007/s11060-016-2059-3
DO - 10.1007/s11060-016-2059-3
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C2 - 26821711
AN - SCOPUS:84955577526
SN - 0167-594X
VL - 127
SP - 535
EP - 539
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 3
ER -
