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Apatinib Plus Temozolomide for Recurrent Glioblastoma: An Uncontrolled, Open-Label Study


Apatinib Plus Temozolomide for Recurrent Glioblastoma: An Uncontrolled, Open-Label Study

Yong Wang et al. Onco Targets Ther.


Objective: This study aimed to determine the efficacy and tolerability of apatinib plus dose-dense temozolomide (TMZ) as first-line treatment for recurrent glioblastoma (rGBM).

Methods: Patients with rGBM were enrolled in this study. Patients were subjected to concurrent treatment of apatinib (500 mg qd) and dose-dense TMZ (100 mg/m2, 7 days on with 7 days off) until disease progression or intolerable toxicity. Efficacy was evaluated using Response Assessment in Neuro-Oncology criteria for high-grade glioma. Safety was assessed using NCI-CTCAE 4.0. Survival was estimated with Kaplan-Meier curve and log rank test.

Results: From March 2016 to January 2018, 20 eligible patients who had relapsed from the standard chemoradiotherapy regimen (TMZ and radiotherapy) were enrolled in this study. The median follow-up time was 12 months. All patients were eligible for efficacy analysis. The objective response rate (ORR) was 45%. The disease control rate (DCR) was 90%. The median progress-free survival time was 6 months (95% CI, 5.3 to 7.8 months). The 6-month progression-free survival rate was 50%. The median overall survival was 9 months (95% CI, 8.2 to 12.2 months). The most common treatment-related adverse events were hypertension (21%), hand-foot syndrome (16%), leukopenia (14%), and thrombocytopenia (12%).

Conclusion: Apatinib combined with dose-dense TMZ was effective in terms of PFS, ORR, and DCR and was well tolerated after appropriate dose reduction in the Chinese population tested. Further randomized controlled clinical studies are needed to confirm the efficacy of apatinib combined with TMZ for treatment of rGBM.

Keywords: apatinib; central nervous system; glioblastoma; recurrence; temozolomide; vascular endothelial growth factor receptor.

Conflict of interest statement

The authors declare that they have no competing interests.


Figure 1
Figure 1
Kaplan–Meier cures of progression-free survival in all patients.
Figure 2
Figure 2
Kaplan–Meier curves of overall survival in all patients.
Figure 3
Figure 3
Brain scan of a patient with rGBM. (A–D) Contrast-enhanced MRI; (E–H) MRI-Flair; (A–D) MRI images followed-up every three months before and after treatment in chronological order. The patient achieved complete remission after treatment and had progression-free survival time of 13 months.

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