Successful treatment using apatinib in intractable brain edema: A case report and literatures review

Abstract

The treatment of intractable vasogenic brain edema (VBE) caused by tumor and irradiation is challenging. Traditional intervention strategy includes dehydration and glucocorticoids accompanied by obvious side effects and minor effects after long-term use. Novel treatment needs to be found urgently. Recently, vascular endothelial growth factor (VEGF)/VEGFR pathway has been revealed to be essential in VBE. Therefore, tyrosine kinase inhibitor (TKI) targeting VEGFR which blocks (VEGF)/VEGFR signal might be effective. However, such reports have seldom been described. Herein, we documented a heavily-treated breast cancer patient experienced progressive aphasia, limb activity disorder and intermittent convulsion 10 months after radiotherapy of brain metastasis (BM). Cranial MRI demonstrated large peritumoral brain edema (PTBE). High dose of steriods and dehydration had no improvement. Apatinib with a dose of 250mg daily was initiated and all her discomforts disappeared after 10 days of use. The brain MRI of taking apatinib 5 weeks demonstrated remarkable shrinkage of edema. Our case indicates that apatinib, a potent small-molecular TKI targeted VEGFR2 is promising for intractable VBE for satisfactory efficacy and safety. This case is of great value in its rarity and because it provides new insight into PTBE management in clinical practice.

Multicenter phase II study of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis

“…Apatinib is another oral TKI that selectively targets VEGFR-2 to inhibit tumor angiogenesis ( 14 ), and apatinib has reported activity in BC ( 15 , 16 ). However, BC with chest wall metastasis (CWM) has a rich blood supply because of the high expression of angiogenic factors.…”

Apatinib and fractionated stereotactic radiotherapy for the treatment of limited brain metastases from primary lung mucoepidermoid carcinoma

“…Hu et al [ 4 ] reported that apatinib could shrink refractory radiation-induced brain edema in patients with NSCLC and NHL, and dramatically improve their symptoms. Song et al [ 5 ] found that apatinib can shrink PTBE in a remarkably short period of time. Li et al [ 17 ] reported that low-dose apatinib monotherapy showed excellent efficacy in the treatment of symptomatic BMs in 1 patient with triple-negative breast cancer.…”

“…[ 3 ] Some case reports have focused on the effects of treatment with apatinib for BM and peritumoral brain edema (PTBE) or radiation-induced brain edema. [ 4 , 5 ] Gene mutation-targeting drugs have a good effect on BM in NSCLC with corresponding gene mutation, however, there are no particularly effective drugs for BM in primary lung MEC. In our present case, we report for the first time that FSRT and apatinib were used in combination to treat a patient with primary lung MEC who had limited BM with PTBE.…”

Blood-Brain Barrier Alterations and Edema Formation in Different Brain Mass Lesions

“…• anti-VEGFR-1 antibody inhibits ECM invasion • PAMs-TLR-2 interaction promotes pro-inflammatory astrocytic activation Esen et al, 2004 • TLR2 promotes pro-inflammatory microglial activation Kielian et al, 2005a • TLR2 regulates pro-inflammatory mediators' expression Kielian et al, 2005b • MyD88 promotes a protective inflammatory response in mouse brain abscess mode and subsequent opening of the BBB (Davies, 2002). Moreover, VEGF may induce fenestration in the endothelium and thus increase capillary permeability partially by inhibiting the TJ proteins claudin-1 and claudin-5 (Roberts and Palade, 1995;Song et al, 2018). Along with metastatic cells, tumor-infiltrating lymphocytes in the peritumoral edema also contribute to VEGF expression.…”