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1.
Neurooncol Pract ; 5(4): 246-250, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30402263

ABSTRACT

BACKGROUND: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor activity shown to enhance overall survival and progression free survival in patients with newly diagnosed glioblastoma (GBM). This reports on the late toxicity of the VPA/radiotherapy (RT)/temozolomide (TMZ) combination in the long-term survivors of a phase 2 study evaluating this regimen. METHODS: 37 patients with newly diagnosed GBM were initially enrolled on this trial and received combination therapy. VPA/RT/TMZ related late toxicities were evaluated in the 6 patients that lived greater than 3 years using the Cancer Therapy and Evaluation Program Common Toxicity Criteria (CTC) Version 4.0 for toxicity and adverse event reporting as well as the RTOG/EORTC Radiation Morbidity Scoring Scheme. RESULTS: The median duration of follow-up for these 6 patients was 69.5m. In this cohort, the median OS was 73.8m (60.8-103.8m) and median PFS was 53.1m (37.3 - 103.8m). The most common late toxicity of VPA in conjunction with RT/TMZ were the CTC classifications of neurological, pain, and blood/ bone marrow toxicity and most were grade 1/2. There were only two grade 3/4 toxicities. CONCLUSIONS: The addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated with little late toxicity. Additionally, VPA may result in improved outcomes as compared to historical data and merits further study.

2.
Int J Radiat Oncol Biol Phys ; 92(5): 986-992, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-26194676

ABSTRACT

PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. METHODS AND MATERIALS: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). RESULTS: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. CONCLUSIONS: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Brain Neoplasms/radiotherapy , Dacarbazine/analogs & derivatives , Glioblastoma/radiotherapy , Radiation-Sensitizing Agents/administration & dosage , Valproic Acid/administration & dosage , Adult , Age Factors , Aged , Antineoplastic Agents, Alkylating/adverse effects , Bone Marrow/drug effects , Bone Marrow/radiation effects , Brain Neoplasms/blood , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Chemoradiotherapy/methods , Chemotherapy, Adjuvant , Dacarbazine/adverse effects , Dacarbazine/therapeutic use , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Female , Glioblastoma/blood , Glioblastoma/drug therapy , Glioblastoma/mortality , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/therapeutic use , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/adverse effects , Radiation-Sensitizing Agents/metabolism , Temozolomide , Time Factors , Valproic Acid/adverse effects , Valproic Acid/blood
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