Wolff Johannes E A, Kramm Christof, Kortmann Rolf-Dieter, Pietsch Torsten, Rutkowski Stefan, Jorch Norbert, Gnekow Astrid, Driever Pablo Hernáiz
Children's Cancer Hospital, Department of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, USA.
J Neurooncol. 2008 Dec;90(3):309-14. doi: 10.1007/s11060-008-9662-x. Epub 2008 Aug 5.
Valproic acid (VPA) inhibits histone deacetylase and has been reported to induce apoptosis in glioma. We report 44 heavily pretreated pediatric patients with high-grade glioma or diffuse intrinsic pontine glioma who received VPA as oral continues maintenance treatment with individual dose adaptation. The tumor status when starting the drug was: no measurable disease in 12, measurable but stable disease in 12, and measurable progressive disease in 22 patients. Average trough blood levels of VPA were 99 mg/l. The most frequent complaint was somnolence (three patients), but no severe toxicity was reported. One relapse patient responded, early progression of disease was observed in three frontline patients and in six relapsed patients. Median overall survival duration for all patients was 1.33 years, with large differences between first-line (5-year overall survival, 44%) and relapse therapy (5-year overall survival, 14%). This shows that valproate is safe in this patient population. The moderate tumor efficacy encourages studying the drug further as an element of multi-agent protocols.
丙戊酸（VPA）可抑制组蛋白脱乙酰酶，据报道能诱导胶质瘤细胞凋亡。我们报告了44例经过大量前期治疗的儿童高级别胶质瘤或弥漫性脑桥内在型胶质瘤患者，他们接受VPA作为口服持续维持治疗，并根据个体剂量进行调整。开始用药时的肿瘤状态为：12例无可测量疾病，12例可测量但疾病稳定，22例可测量的疾病进展。VPA的平均谷血浓度为99mg/l。最常见的主诉是嗜睡（3例患者），但未报告严重毒性。1例复发患者有反应，3例一线患者和6例复发患者出现疾病早期进展。所有患者的中位总生存期为1.33年，一线治疗（5年总生存率44%）和复发治疗（5年总生存率14%）之间存在较大差异。这表明丙戊酸盐在该患者群体中是安全的。其适度的肿瘤疗效鼓励进一步研究将该药物作为多药联合方案的一个组成部分。
