apatinib and Glioblastoma

Adult brainstem gliomas are characterized into subtypes depending on clinicopathologic and radiographic characteristics. Among them, brainstem glioblastoma is the most malignant and has the poorest prognosis, with surgical resection for this condition posing a great challenge and risk. Postoperative synchronous radiotherapy and temozolomide (TMZ) chemotherapy, or "Stupp's regimen", is the standard of care for glioblastomas. However, antiangiogenic therapy, which is widely used for different cancers, is now an alternative treatment for malignant tumors. Angiogenesis is one of the pathological features of glioblastoma and is involved in tumor progression and metastasis. Besides, previous studies suggested a better response to antiangiogenic therapy in some solid tumors with TP53 mutation than TP53 wide-type. Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that mainly targets vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit angiogenesis. In addition, apatinib can cross the blood-brain barrier and improve encephaledema. This report describes the use of concurrent apatinib and dose-dense TMZ in a clinically inoperable patient who had a refractory brainstem glioblastoma with a TP53 germline mutation. He obtained an ongoing progression free survival (PFS) of nearly 16.0 months after resistance to TMZ maintenance. Due to the patient's circumstances, apatinib and TMZ was considered an effective and safe treatment method.

Topics: Adult; Brain Neoplasms; Brain Stem; Dacarbazine; Glioblastoma; Humans; Male; Pyridines; Temozolomide

Glioblastoma is a cranial malignant tumor with a high recurrence rate after surgery and a poor response to chemoradiotherapy. Bevacizumab has demonstrated efficacy in the treatment of glioblastoma by inhibiting vascular endothelial growth factor, but the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors varies in treating glioblastoma. This single-arm prospective study aimed to explore the efficacy and safety of the vascular endothelial growth factor receptor tyrosine kinase inhibitor apatinib in treating recurrent glioblastoma after chemoradiotherapy.. A total of 15 patients with recurrent glioblastoma (2016 World Health Organization grade IV) after chemoradiotherapy were enrolled in this study from September 2017 to September 2019 and treated with apatinib 500 mg once daily. Responses were evaluated according to the Response Assessment in Neuro-Oncology criteria, and adverse events were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.. The overall response rate was 33.3%, and the disease control rate was 66.6%. The median progression-free survival was 2 months, and the median overall survival was 6.5 months. The apatinib dose was adjusted in seven patients because of adverse events (46.6%). The most common adverse events were thrombocytopenia (53.3%), asthenia (40%), and hand-foot syndrome (33.3%).. Apatinib might be effective in treating recurrent glioblastoma after chemoradiotherapy in terms of the overall response rate, but the efficacy is not durable and the clinical benefit is limited. The adverse effects of apatinib were acceptable.. ChiCTR-ONC-17013098, date of registration: 24 October, 2017.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Bevacizumab; Glioblastoma; Humans; Prospective Studies; Vascular Endothelial Growth Factor A

Glioblastoma is the most common malignant tumor of the central nervous system, which originates from glial cells and corresponding precursors. Due to its strong invasion and rapid growth, the prognosis of patients after treatment is very poor and easy to relapse.. In August 2015, a 48 years old man with a relapse of glioblastoma.. The patient was diagnosed by computed tomography, magnetic resonance imaging, and pathological biopsy in this case report.. The patient underwent 2 surgeries, radiotherapy, and multiple regular chemotherapy sessions over the next 6 years. Apatinib, an inhibitor of vascular endothelial growth factor receptor 2 was given to treat recurrent glioma.. It was found that radiotherapy combined with temozolomide administration often increased the size of the original lesion or produced a new glioblastoma lesion. The lesion development was similar to tumor progression, which was called pseudoprogression. And it significantly prolonged the survival of this patient.. Surgery, radiotherapy and chemotherapy with apatinib and temozolomide are effective to treat the patients with pseudoprogression in glioblastoma.

Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Glioblastoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Temozolomide

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) is a subunit of Complex I of the mitochondrial respiratory chain, which is important in metabolic reprogramming and oxidative stress in multiple cancers. However, the biological role and molecular regulation of NDUFA4L2 in glioblastoma (GBM) are poorly understood. Here, we found that NDUFA4L2 was significantly upregulated in GBM; the elevated levels were correlated with reduced patient survival. Gene knockdown of NDUFA4L2 inhibited tumor cell proliferation and enhanced apoptosis, while tumor cells initiated protective mitophagy in vitro and in vivo. We used lentivirus to reduce expression levels of NDUFA4L2 protein in GBM cells exposed to mitophagy blockers, which led to a significant enhancement of tumor cell apoptosis in vitro and inhibited the development of xenografted tumors in vivo. In contrast to other tumor types, NDUFA4L2 expression in GBM may not be directly regulated by hypoxia-inducible factor (HIF)-1α, because HIF-1α inhibitors failed to inhibit NDUFA4L2 in GBM. Apatinib was able to effectively target NDUFA4L2 in GBM, presenting an alternative to the use of lentiviruses, which currently cannot be used in humans. Taken together, our data suggest the use of NDUFA4L2 as a potential therapeutic target in GBM and demonstrate a practical treatment approach.

Topics: Animals; Cell Proliferation; Disease Progression; Electron Transport Complex I; Glioblastoma; Humans; Male; Mice; Mice, Nude; Pyridines; Transfection

Apatinib, a novel tyrosine kinase inhibitor, has anti-angiogenetic effect just as bevacizumab. Although bevacizumab has been used successfully in treating cerebral radiation necrosis, there has yet not any report on that apatinib can treat pseudoprogression with symptoms. Here we report a case of glioblastoma multiforme (GBM) patient with pseudoprogression after receiving the concurrent chemoradiotherapy, which was successfully treated by apatinib. A 51-year-old woman had multiple intracranial lesions (left parietal and right frontal), the primary left parietal lesion was surgically removed and was pathologically confirmed as glioblastoma (WHO grade IV). Then the patient received postoperative temozolomide with concurrent chemoradiotherapy. Three weeks after the radiotherapy, the patient experienced increased intracranial pressure and seizure. Magnetic resonance imaging (MRI) T1 enhancement examination showed an increase of abnormal enhancement range in the area of irradiation. After multiple disciplinary team (MDT) discussion, the patient was diagnosed with pseudoprogression after radiotherapy. Then she was given apatinib for 8 weeks at a dose of 500 mg qd. During the treatment period, the clinical symptoms and corresponding nerve images of the patient have been rapidly improved. In 12 months after the radiotherapy, progression of tumor in the primary site has not been discovered. Apatinib showed a good therapeutic effect and tolerance for the development of pseudoprogression advances with obvious symptoms.

Topics: Antineoplastic Agents; Brain Neoplasms; Female; Glioblastoma; Humans; Middle Aged; Pyridines