Abstract
Anti-angiogenic therapy, targeting vascular endothelial growth factor (VEGF)-A/VEGF receptors (VEGFRs), is beneficial for tumor growth prevention in a malignant glioma. A simultaneous blockade using both bevacizumab (Bev), which targets circulating VEGF-A, and a multi-kinase inhibitor on VEGFRs was more effective for advanced solid cancers, including melanoma and renal cell carcinoma. However, previous clinical trials demonstrated a high adverse event rate. Additionally, no studies previously assessed treatment efficacy and safety using both VEGF-A and VEGFR-targeted agents for malignant gliomas. We had conducted clinical trials investigating VEGFRs peptide vaccination in patients with malignant gliomas, in which the treatment exhibited safety and yielded therapeutic effects in some patients. The combined use of Bev and VEGFRs vaccination may enhance the anti-tumor effect in malignant gliomas. In this pilot study, the adverse event profile in patients treated with Bev after the vaccination was investigated to establish this treatment strategy, in comparison to those treated with Bev collected from the published data or treated with the vaccination alone. In our previous clinical studies on patients with malignant gliomas, Bev was administered to 13 patients after VEGFRs vaccinations. One patient had a Grade 4 pulmonary embolism. Two patients had Grade 2 cerebral infarctions. There were no significant differences in the adverse event rates among patients treated with Bev, with the vaccination, or with Bev after the vaccination. Although careful observation is imperative for patients after this combination treatment strategy, VEGFRs-targeted vaccination may coexist with Bev for malignant gliomas.
Highlights
A glioblastoma is the most aggressive primary brain tumor
The vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR) signaling are strongly upregulated, and the degree of expression correlates with the grade of malignancy and prognosis of the glioblastomas [2,3,4,5]
In the Vac + Bev group, Bev was administered to 13 patients after the VEGFRs vaccinations
Summary
A glioblastoma is the most aggressive primary brain tumor. The current standard treatment after surgical resection, which includes radiotherapy and chemotherapy with temozolomide, provides a limited degree of improvement in survival rate, with a median overall survival of 15 months [1].Glioblastomas exhibit extensive vascularity. A glioblastoma is the most aggressive primary brain tumor. The current standard treatment after surgical resection, which includes radiotherapy and chemotherapy with temozolomide, provides a limited degree of improvement in survival rate, with a median overall survival of 15 months [1]. The vascular endothelial growth factor (VEGF)-A and VEGF receptor (VEGFR) signaling are strongly upregulated, and the degree of expression correlates with the grade of malignancy and prognosis of the glioblastomas [2,3,4,5]. Vaccines 2020, 8, 498 signaling seems to be an attractive target for anti-angiogenic therapy in glioblastomas. Bevacizumab (Bev), which targets circulating VEGF-A; multi-kinase inhibitors such as cediranib, which target
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