Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

被引：154

作者：

Happold, Caroline ^{[1
]}

Gorlia, Thierry ^{[3
]}

Chinot, Olivier ^{[4
]}

Gilbert, Mark R. ^{[5
]}

Nabors, L. Burt ^{[6
]}

Wick, Wolfgang ^{[7
,8
]}

Pugh, Stephanie L. ^{[9
]}

Hegi, Monika ^{[2
]}

Cloughesy, Timothy ^{[10
]}

Roth, Patrick ^{[1
]}

Reardon, David A. ^{[11
]}

Perry, James R. ^{[12
]}

Mehta, Minesh P. ^{[13
]}

Stupp, Roger ^{[1
]}

Weller, Michael ^{[1
]}

机构：

[1] Univ Zurich Hosp, CH-8091 Zurich, Switzerland

[2] Univ Lausanne Hosp, Lausanne, Switzerland

[3] Eortc Data Ctr, Brussels, Belgium

[4] Aix Marseille Univ, Marseille, France

[5] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[6] Univ Alabama Birmingham, Birmingham, AL USA

[7] Heidelberg Univ, Heidelberg, Germany

[8] German Canc Res Ctr, Heidelberg, Germany

[9] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA

[10] Univ Calif Los Angeles, Neurooncol Program, Los Angeles, CA USA

[11] Dana Farber Canc Inst, Boston, MA 02115 USA

[12] Univ Toronto, Toronto, ON, Canada

[13] Univ Maryland, Baltimore, MD 21201 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2016年 / 34卷 / 07期

关键词：

STANDARD TREATMENT; RADIATION-THERAPY; BRAIN-TUMORS; OPEN-LABEL; TEMOZOLOMIDE; EPILEPSY; CHEMOTHERAPY; BEVACIZUMAB; IRRADIATION; COMBINATION;

D O I：

10.1200/JCO.2015.63.6563

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of anti-epileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use. Conclusion The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials. (C) 2016 by American Society of Clinical Oncology

引用

页码：731 / +

页数：16

共 24 条

[1] Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival [J].