Schiavetti Amalia, Varrasso Giulia, Mollace Maria Giovanna, Dominici Carlo, Ferrara Eva, Papoff Paola, Di Biasi Claudio
Department of Pediatrics, "Sapienza" University, Viale Regina Elena 324, 00161, Rome, Italy.
Department of Radiology Emergency, "Sapienza" University, Rome, Italy.
Childs Nerv Syst. 2019 Jun;35(6):1007-1012. doi: 10.1007/s00381-019-04117-z. Epub 2019 Mar 21.
The aim of the study is to assess tumor response, treatment-related toxicities, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory brain tumors treated with bevacizumab-containing regimen.
Patients that had received I and II line treatments with or without megatherapy were included. Doses and schedule were as follows: bevacizumab (BVZ) 10 mg/kg i.v. with irinotecan (IRI) 150 mg/m i.v. every 2 weeks ± temozolamide (TMZ) 200 mg/m p.o. daily for 5 days every 4 weeks. TMZ was omitted in heavily pretreated cases.
Between 2013 and 2018, 12 patients (3F/9M), median age 161 months (range 66-348), affected with medulloblastoma (n 7), or low-grade glioma (n 2), or high-grade glioma (n 3), received BVZ/IRI association (median courses 20, range 4-67); 3 of them continued single-agent BVZ (median courses 23, range 8-39). TMZ (median courses 8, range 2-26) was administered in eight patients and then stopped in three of them because of myelotoxicity or lack of compliance. Treatment was well tolerated. After 3 months, two complete responses, two partial responses, seven stable diseases, and one progressive disease were observed. Nine cases experienced an improvement in neurological symptoms. Median time to progression was 11 months (95% confidence interval, 4-18 months). Six-month and 2-year PFS were 75% and 42%, respectively. The OS is 33%; interestingly, two cases (one medulloblastoma and one high-grade glioma) are progression-free off-therapy since 30 and 48 months, respectively.
BVZ/IRI association ± TMZ showed encouraging therapeutic activity and low toxicity in this series of relapsed/refractory brain tumors.
本研究旨在评估接受含贝伐单抗方案治疗的复发/难治性脑肿瘤患者的肿瘤反应、治疗相关毒性、无进展生存期（PFS）和总生存期（OS）。
纳入接受过一线和二线治疗（有或无大剂量化疗）的患者。剂量和给药方案如下：贝伐单抗（BVZ）10mg/kg静脉注射，伊立替康（IRI）150mg/m²静脉注射，每2周一次，±替莫唑胺（TMZ）200mg/m²口服，每天一次，共5天，每4周重复。在预处理严重的病例中省略TMZ。
2013年至2018年期间，12例患者（3例女性/9例男性），中位年龄161个月（范围66 - 348个月），患有髓母细胞瘤（n = 7）、低级别胶质瘤（n = 2）或高级别胶质瘤（n = 3），接受了BVZ/IRI联合治疗（中位疗程20，范围4 - 67）；其中3例继续使用单药BVZ（中位疗程23，范围8 - 39）。8例患者接受了TMZ治疗（中位疗程8，范围2 - 26），其中3例因骨髓毒性或依从性差而停药。治疗耐受性良好。3个月后，观察到2例完全缓解、2例部分缓解、7例病情稳定和1例病情进展。9例患者神经症状有所改善。中位进展时间为11个月（95%置信区间，4 - 18个月）。6个月和2年的PFS分别为75%和42%。OS为33%；有趣的是，2例患者（1例髓母细胞瘤和1例高级别胶质瘤）分别在30个月和48个月后停止治疗且无疾病进展。
在这一系列复发/难治性脑肿瘤中，BVZ/IRI联合±TMZ显示出令人鼓舞的治疗活性和低毒性。
