A phase II clinical trial evaluating the efficacy and safety of apatinib combined with dose-dense temozolomide in recurrent glioblastoma

Abstract

Abstract Background Glioblastoma (GBM) is well known as the most common primary aggressive malignant brain tumor of the CNS and became one of the most lethal forms of cancer in human. The prognosis for patients with GBM is very poor. Current treatment options for recurrent GBM are very limited. Apatinib, a novel small molecular anti-angiogenic inhibitor, can highly selectively bind VEGFR-2 and inhibit its activation to block VEGF mediated the signal transduction and inhibit the angiogenesis to control the growth of the tumors. We hypothesized that apatinib combined with dose-dense TMZ could lead to prolonged 6-month PFS and/or OS. We also assessed toxicity and tolerability. Methods Patients with recurrent glioblastoma were enrolled in this study. Patients were treated with concurrent treatment of apatinib (500mg qd) and dose-dense temozolomide (100\xa0mg/m2 , 7 days on with 7 days off ) until disease progression or intolerable toxicity. The efficacy was evaluated using RANO high-grade glioma criteria. The safety was assessed via NCI-CTCAE 4.0. Survival was estimated with Kaplan-Meier curve and log-rank test. Results From March 2016 to January 2018, twenty eligible patients who had relapsed from the standard chemoradiotherapy regimen were enrolled in this study. 35% were female and the median ages were 50.5 years. The median KPS score before treatment was 70. Median follow-up time was 12 months. KPS scores improved in 60%(12/20) of patients after treatment. In total, there were 1 with CR, 8 with PR, 9 with SD, and 2 with PD. Three patients were still alive. The ORR was 45% (9/20) and the DCR was 90% (18/20). The median PFS for all patients were 6 months (95% confidence interval [CI]: 5.3m to 7.8m). Median OS is 9.3 months (95% CI, 8.2m–12.2m). The most common treatment-related adverse events (AEs) were hypertension (20.9%), hand-foot syndrome (16.3%), leukopenia (14.0%), The grade 3/4 adverse events included hypertension (4.7%), leukopenia (2.3%), thrombocytopenia (2.3%). Conclusions Apatinib combined with dose-dense temozolomide seems to be a promising therapeutic option for recurrent glioblastoma with acceptable toxicity profiles. Clinical randomized controlled trial is warranted to be designed to confirm the results. Clinical trial identification NCT03660761. Editorial acknowledgement Baoyan Liu (Shandong Medical Biotechnological Center, School of Medicine and Life Science, Shandong Academy of Medical Sciences, University of Jinan) provided assistance with manuscript editing. Legal entity responsible for the study Shandong Cancer Hospital. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.