A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.
A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.
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DOI：
10.1007/s11060-016-2195-9
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发表时间：
2016-09
影响因子：
3.9
通讯作者：
de Groot, John F.
中科院分区：
文献类型：
--
作者：
Weathers, Shiao-Pei;Han, Xiaosi;Liu, Diane D.;Conrad, Charles A.;Gilbert, Mark R.;Loghin, Monica E.;O'Brien, Barbara J.;Penas-Prado, Marta;Puduvalli, Vinay K.;Tremont-Lukats, Ivo;Colen, Rivka R.;Yung, W. K. Alfred;de Groot, John F.
抗血管生成治疗可迅速降低血管通透性和脑水肿，但高剂量贝伐单抗可诱导选择性压力促进抵抗。该试验评估了低剂量贝伐单抗联合洛莫司汀（CCNU）与标准剂量贝伐单抗在复发性胶质母细胞瘤患者中的疗效。既往接受放疗和替莫唑胺治疗的复发性胶质母细胞瘤患者（N = 71）按1:1随机分配，接受贝伐单抗单药治疗（10 mg/kg）或低剂量贝伐单抗（5 mg/kg）联合洛莫司汀（90 mg/m2）。主要终点是无进展生存期（PFS），基于使用RANO标准对对比后t1加权和非对比T2/FLAIR加权磁共振成像（MRI）进行盲法独立放射学评估。在69例可评估的患者中，低剂量贝伐单抗+洛莫司汀组的中位PFS（4.34个月，CI: 2.96-8.34）与贝伐单抗单独组（4.11个月，CI: 2.69-5.55, p = 0.19）相比并没有显著延长。在首次复发的患者中，与贝伐单抗单独治疗组（3.22个月CI: 2.5-6.01, p = 0.08）相比，低剂量贝伐单抗+洛莫司汀组（4.96个月，CI: 4.17-13.44）有更长中位PFS时间的趋势。在复发性胶质母细胞瘤患者中，低剂量贝伐单抗联合洛莫司汀并不优于标准剂量贝伐单抗。虽然该研究不是专门用于评估首次复发的患者，但在低剂量贝伐单抗加洛莫司汀的亚组中，PFS改善的趋势很强。需要进一步的研究来更好地确定可能从联合治疗中获益最多的亚组。
Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m2). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI: 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI: 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI: 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI: 2.5-6.01, p = 0.08). The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment.
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