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Pediatr Blood Cancer:放疗联合VPA和贝伐珠单抗治疗胶质瘤的耐受性良好

2021-12-16 MedSci原创 MedSci原创

高等级胶质瘤(HGG)和弥漫性固有树胶质瘤(DIPG)的预后仍然不乐观。理论上同时使用具有抗胶质瘤和放射增敏作用的药物应能改善HGG和DIPG的疗效。丙戊酸(VPA)是一种在儿童中使用了30多年的抗惊

高等级胶质瘤(HGG)和弥漫性固有树胶质瘤(DIPG)的预后仍然不乐观。理论上同时使用具有抗胶质瘤和放射增敏作用的药物应能改善HGG和DIPG的疗效。丙戊酸(VPA)是一种在儿童中使用了30多年的抗惊厥药,可以抑制组蛋白去乙酰化酶(HDAC),贝伐珠单抗是一种针对人血管内皮生长因子-A同种型的人源化单克隆IgG抗体,已被批准作为成人胶质母细胞瘤的治疗方法。新的一项2期临床试验中,研究人员评估了VPA和放疗,然后再用VPA和贝伐珠单抗治疗新诊断的DIPG或HGG患儿的疗效和耐受性,研究结果已发表于Pediatr Blood Cancer。


从2009年9月至2015年8月,研究纳入38名3~21岁的DIPG和HGG儿童患者(DIPG组20名,HGG组18名),接受放疗和VPA,剂量为15mg/kg/天,并调整剂量以维持在85~115μg/mL的谷值范围。放射后继续使用VPA,并在完成放疗后四周开始使用贝伐单抗,剂量为10 mg/kg,每两周静脉注射一次。

结果显示,在放疗和VPA期间,需要停止或修改VPA剂量的≥3级不良反应包括3级血小板减少(1)、3级体重增加(1)和3级胰腺炎(1)。在VPA和贝伐单抗期间,最常见的≥3级不良反应是3级中性粒细胞减少(3),3级血小板减少(3),3级疲劳(3)和3级高血压(4)。两名患者在疾病进展前停止了方案治疗(一名4级血栓形成,一名1级腔内出血)。

DIPG组中位无事件生存期(EFS)和总生存期(OS)分别为7.8(95% CI 5.6-8.2)和10.3(7.4-13.4)个月,估计一年EFS为12%(2%-31%)。HGG组中位EFS和OS分别为9.1(6.4-11)和12.1(10-22.1)个月,估计一年EFS为24%(7%-45%)。4例胶质母细胞瘤和错配修复缺陷综合征患者的EFS分别为28.5、16.7、10.4和9个月。


综上所述,该研究结果表明,放疗联合VPA和贝伐珠单抗的耐受性良好,但是似乎并不能改善DIPG或HGG儿童的EFS或OS。

原始出处:

Jack Meng-Fen Su, et al., A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high-grade glioma. Pediatr Blood Cancer. 2020 Jun;67(6):e28283. doi: 10.1002/pbc.28283.

 

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