丙戊酸增效高级别胶质细胞瘤术后放化疗临床观察

Valproic acid combined with chemoradiotherapy improves the survival of patients with high grade gliomas

目的分析高级别胶质细胞瘤术后放化疗同时应用丙戊酸(VPA)抗癫痫药对患者预后的影响。方法回顾性分析171例原发性高级别胶质细胞瘤患者,分为放化疗组[术后放疗同步尼莫司汀(ACNU)间质化疗、替莫唑胺(TMZ)口服化疗; VPA联合放化疗组(术后放疗同步ACNU与TMZ化疗联合VPA治疗)],VPA治疗少于3个月或无VPA治疗者纳入前组,大于3个月者纳入后组,分析两组癫痫的发生率、总生存期(OS)及不良反应。结果术后放化疗期间接受VPA防治癫痫的有124例(72. 5%),有癫痫发作史的患者92例(53. 8%),其中69例(75. 0%)癫痫得到完全控制。VPA联合放化疗组94例,中位OS为26个月,放化疗组77例,中位OS为20个月(P=0. 023);[风险比(HR):1. 48; 95%置信区间(CI):1. 08～2. 05; P=0. 016]。常见的不良反应为骨髓抑制、消化道反应、肝功能损害,两组患者不良反应的表现及发生率相近。结论高级别胶质细胞瘤术后放化疗期间规律应用VPA既可防治癫痫又可有效改善患者OS,作用安全,并且VPA和肿瘤病理分级作为独立的预后因素可影响患者的生存期。

Objective The efficacy of valproic acid(VPA)combined with chemoradiotherapy on post-operative survival of patients with high grade gliomas was investigated.Methods A retrospective analysis of171patients with high grade glioma was conducted to study the efficacy and toxicity of VPA on the outcome.The outcome of VPA combined with chemoradiotherapy was analyzed in 94(55.0%)patients with a minimum polytherapy of3months and77(45.0%)patients receiving VPA less than3months or no VPA treatment.Results A total of 124(72.5%)patients were taking VPA during treatment and seizures were noted in 92(53.8%)patients.Seizure freedom was achieved in 75.0%(69/92)on VPA alone.Median overall survival(OS)of patients receiving VPA more than3months was 26 months(vs 20 months for patients not receiving VPA or shorter than3months)(P=0.023)[hazard ratio(HR):1.48;95%confidence interval(CI):1.08~2.05;P=0.016].The most common adverse reactions were myelosuppression,gastrointestinal reactions and liver damage during the treatment.Performance and incidence of adverse reactions were similar in two groups.Conclusion Administration of VPA as an adjunct to chemoradiotherapy not only controls the epilepsy,but also prolongs the overall survival safely and improve the prognosis significantly.