A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma

被引:56
作者
Weathers, Shiao-Pei [1 ]
Han, Xiaosi [2 ]
Liu, Diane D. [3 ]
Conrad, Charles A. [1 ,5 ]
Gilbert, Mark R. [1 ,6 ]
Loghin, Monica E. [1 ]
O'Brien, Barbara J. [1 ]
Penas-Prado, Marta [1 ]
Puduvalli, Vinay K. [1 ,7 ]
Tremont-Lukats, Ivo [1 ,8 ]
Colen, Rivka R. [4 ]
Yung, W. K. Alfred [1 ]
de Groot, John F. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, 1515 Holcombe Blvd,Unit 431, Houston, TX 77030 USA
[2] Univ Alabama Birmingham, 1020 Fac Off Tower,510 20th St South, Birmingham, AL 35294 USA
[3] Univ MD Anderson Canc Ctr, Dept Biostat, 1400 Pressler St, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Neuroradiol, 1400 Pressler St Unit 1482, Houston, TX 77030 USA
[5] Texas Oncol, 901 W 38th St, Austin, TX 78705 USA
[6] NIH, 9030 Old Georgetown Rd, Bethesda, MD 20892 USA
[7] M410 Starling Loving Hall,320 W,10th Ave, Columbus, OH 43210 USA
[8] Houston Methodist Hosp, Dept Neurosurg, 6560 Fannin,Scurlock Suite 900, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
Glioblastoma; Bevacizumab; Lomustine; Angiogenesis; VEGF; NEWLY-DIAGNOSED GLIOBLASTOMA; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; MALIGNANT GLIOMA; TEMOZOLOMIDE; COMBINATION; IRINOTECAN; NORMALIZATION; CHEMOTHERAPY; PROGRESSION;
D O I
10.1007/s11060-016-2195-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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/m(2)). 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.
引用
收藏
页码:487 / 494
页数:8
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