目的:弥漫性中线胶质瘤(DMG),H3K27M突变体是一种弥漫性高级别神经胶质瘤,发生在大脑中线,在尽最大努力的手术下预后极差,辐射,和其他疗法。为了更好的治疗,我们探讨了阿帕替尼和替莫唑胺联合治疗DMG的新疗法的疗效和毒性.
方法:回顾性分析32例接受阿帕替尼联合替莫唑胺治疗的DMG患者。成人给予阿帕替尼500毫克,每天一次250毫克儿科患者。根据标准5/28天方案,以200mg/m2/d施用替莫唑胺。主要临床资料包括患者的基本情况,肿瘤的放射学和病理学特征,治疗,不良反应,预后。
结果:客观反应率为24.1%,疾病控制率为79.3%。所有患者的中位PFS为5.8个月,中位OS为10.3个月。总共有236个治疗周期可用于安全性评估,联合治疗的毒性相对较好。最常见的3级毒性是骨髓抑制,包括白细胞减少症(5.08%)。中性粒细胞减少症(4.24%),淋巴细胞减少(2.12%),血小板减少症(1.69%)和贫血(1.27%)。4级毒性包括中性粒细胞减少症(2.12%),血小板减少(2.12%)和蛋白尿(1.69%)。所有不良反应均在对症治疗或减量后缓解。
结论:阿帕替尼联合替莫唑胺可能是一种有效的方案,毒性可控,疗效良好,可能优于替莫唑胺单药治疗,特别是在新诊断的成年人与位于脑桥外的肿瘤。这种新疗法值得在成年DMG患者中进一步研究。
OBJECTIVE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG.
METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis.
RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction.
CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.