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Clinical Trial
. 2016 Sep;129(3):487-494.
doi: 10.1007/s11060-016-2195-9. Epub 2016 Jul 12.

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

Shiao-Pei Weathers  1 , Xiaosi Han  2 , Diane D Liu  3 , Charles A Conrad  4   5 , Mark R Gilbert  4   6 , Monica E Loghin  4 , Barbara J O'Brien  4 , Marta Penas-Prado  4 , Vinay K Puduvalli  4   7 , Ivo Tremont-Lukats  4   8 , Rivka R Colen  9 , W K Alfred Yung  4 , John F de Groot  4
Affiliations
Clinical Trial

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

Shiao-Pei Weathers et al. J Neurooncol. 2016 Sep.

Abstract

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.

Keywords: Angiogenesis; Bevacizumab; Glioblastoma; Lomustine; VEGF.

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Figures

Figure 1
Figure 1
Trial profile
Figure 2
Figure 2
Median PFS per Blinded Radiology Evaluation by Treatment Arms
Figure 3
Figure 3
Median PFS per Blinded Radiology Evaluation by Treatment Arms in Patients with 1st Recurrence
Figure 4
Figure 4
Median OS in Patients with First Recurrence
See this image and copyright information in PMC

References

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