A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid For Patients With Glioblastoma
Autor: | Andra Krauze, Philip J. Tofilon, Joanna Shih, Michael G. Chang, Kevin Camphausen, Howard A. Fine, Diane Holdford, Sten D. Myrehaug, Sharon M. Smith |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Radiation-Sensitizing Agents Time Factors medicine.medical_treatment Phases of clinical research Kaplan-Meier Estimate Radiation Tolerance Article Disease-Free Survival Drug Administration Schedule Bone Marrow Internal medicine Temozolomide Medicine Humans Radiology Nuclear Medicine and imaging Adverse effect Antineoplastic Agents Alkylating Aged Valproic Acid Chemotherapy Radiation business.industry Brain Neoplasms Age Factors Cancer Chemoradiotherapy Middle Aged medicine.disease Surgery Radiation therapy Dacarbazine Histone Deacetylase Inhibitors Chemotherapy Adjuvant Toxicity Multivariate Analysis Disease Progression lipids (amino acids peptides and proteins) Female business Glioblastoma medicine.drug |
Popis: | 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. |
Databáze: | OpenAIRE |
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