Corresponding author: Sri Gururangan, MRCP, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Hanes House, Room 307, 330 Trent Drive, Box 102382, Durham, NC 27710.
Neuro Oncol. 2014 Jan;16(2):310-7. doi: 10.1093/neuonc/not154. Epub 2013 Dec 4.
A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.
Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9).
Thirty-five evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2-26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1-17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1-2 hypertension in 24, grades 1-2 fatigue in 23, grades 1-2 epistaxis in 18, and grades 1-4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037).
The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.
一项贝伐珠单抗（BVZ）联合伊立替康（CPT-11）治疗复发性低级别胶质瘤的 II 期研究旨在测量持续缓解和/或持续 6 个月以上的稳定疾病以及无进展生存期。
35 例可评估患者每 2 周接受 2 剂（每剂 10mg/kg）单药 BVZ 静脉注射，然后每 2 周接受 BVZ+CPT-11，直至疾病进展、无法耐受毒性或最多 2 年的治疗。相关研究包括神经影像学和肿瘤血管生成标志物（血管内皮生长因子[VEGF]、VEGF 受体 2、缺氧诱导因子 2α 和碳酸酐酶 9）的表达。
35 例可评估患者（中位年龄 8.4 岁[范围，0.6-17.6]）接受了中位 12 个疗程的 BVZ+CPT-11（范围，2-26）。35 例患者中有 29 例（83%）接受了至少 6 个月的治疗。8 例患者在中位时间 5.4 个月（范围，1-17.8）时治疗进展。6 例（17.7%）仍在随访中的患者在无额外治疗的情况下疾病稳定，从开始治疗起中位时间为 40.1 个月（范围，30.6-49.3）。6 个月和 2 年的无进展生存率分别为 85.4%（SE ± 5.96%）和 47.8%（SE ± 9.27%）。与 BVZ 相关的最常见毒性包括 24 例 1-2 级高血压、23 例 1-2 级疲劳、18 例 1-2 级鼻出血和 15 例 1-4 级蛋白尿。基线和第 15 天（P<.0001）及整个治疗期间（P<.037），增强容积中位数均显著下降。
BVZ+CPT-11 联合治疗似乎可使一些复发性低级别胶质瘤患儿获得持续的疾病控制。
