Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Pediatr Blood Cancer. 2010 May;54(5):681-6. doi: 10.1002/pbc.22409.
Bevacizumab, an antibody to the vascular endothelial growth factor, has demonstrated anti-cancer activity in a number of solid tumors. Fear of intratumoral hemorrhage, however, has slowed its introduction into the treatment of central nervous system (CNS) tumors. Currently, only a small number of children with gliomas received bevacizumab.
We retrospectively analyzed 30 patients who received bevacizumab between January 2007 and August 2009. The median age at start of bevacizumab treatment was 9.9 years (range: 1.5-18). Most patients had recurrent/progressive disease, 25 high-grade and 5 low-grade tumors. The median dose of bevacizumab was 9.5 mg/kg (range 5-15 mg/kg) every 2-3 weeks. In total, 478 courses were administered (median/patient 15.9, range: 2-52). The median duration of bevacizumab treatment was 10.0 months (range: 1.6-30.4). Twenty-nine of 30 patients received additional therapy concomitant to bevacizumab.
No bevacizumab related intratumoral hemorrhage occurred in any of our 30 patients. Grade III hypertension was seen in two patients. One patient developed nephrotic syndrome requiring cessation of treatment. Grade III and I proteinuria were observed in one and five patients, respectively. New onset lymphopenia occurred in 12/30 and new onset hypothyroidism in 7/30 patients. Impaired wound healing was manageable. No immediate bevacizumab-related cardiotoxicity was observed as evidenced by echocardiography.
Bevacizumab appears to be safe for children with primary CNS tumors. Adverse effects did occur but were manageable. No treatment-related death occurred. Long-term monitoring is advisable to detect lymphopenia and hypothyroidism. Hypertension occurred less frequently than in adult patients. Further prospective studies including more patients are warranted.
贝伐单抗是一种针对血管内皮生长因子的抗体，已在多种实体瘤中显示出抗癌活性。然而，由于担心肿瘤内出血，其在中枢神经系统（CNS）肿瘤治疗中的应用进展缓慢。目前，只有少数儿童脑胶质瘤患者接受贝伐单抗治疗。
我们回顾性分析了 2007 年 1 月至 2009 年 8 月期间接受贝伐单抗治疗的 30 例患者。开始贝伐单抗治疗时的中位年龄为 9.9 岁（范围：1.5-18 岁）。大多数患者患有复发性/进行性疾病，25 例为高级别肿瘤，5 例为低级别肿瘤。贝伐单抗的中位剂量为 9.5mg/kg（范围 5-15mg/kg），每 2-3 周 1 次。共给予 478 个疗程（中位数/患者 15.9，范围：2-52）。贝伐单抗治疗的中位持续时间为 10.0 个月（范围：1.6-30.4）。30 例患者中有 29 例在接受贝伐单抗治疗的同时接受了其他治疗。
在我们的 30 例患者中，没有一例出现与贝伐单抗相关的肿瘤内出血。有 2 例患者出现 3 级高血压。1 例患者发生肾病综合征，需要停止治疗。1 例和 5 例患者分别出现 3 级和 1 级蛋白尿。30 例患者中有 12 例出现新发性淋巴细胞减少症，7 例出现新发性甲状腺功能减退症。伤口愈合受损是可以控制的。超声心动图未发现与贝伐单抗相关的即时心脏毒性。
贝伐单抗似乎对原发性中枢神经系统肿瘤儿童是安全的。虽然确实出现了不良反应，但是可以控制的。没有与治疗相关的死亡病例发生。建议进行长期监测，以检测淋巴细胞减少症和甲状腺功能减退症。高血压的发生频率低于成人患者。需要进一步进行包括更多患者的前瞻性研究。
