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Onco Targets Ther ; 12: 10579-10585, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819537


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.

World Neurosurg ; 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30639490


BACKGROUND: Invasive pituitary adenomas often recurred after postoperative radiotherapy and are difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum and has been reported to reduce pituitary tumor size and hormone hypersecretion, However, this is far from enough. Pituitary adenomas have relatively high expression of vascular endothelial growth factor. Therefore, antiangiogenic agent has been used in a small number of aggressive or malignant pituitary tumors after recurrence. Apatinib (YN968D1) is a small-molecule antiangiogenic agent that selectively inhibits VEGFR-2 and also mildly inhibits c-Kit and c-Src tyrosine kinases, abundant in invasive pituitary adenomas. CASE PRESENTATION: present a 41-year-old female with a growth hormone (GH)-secreting invasive pituitary adenoma causing menstrual disorder and headache symptoms. Over three years, she underwent four surgeries and a stereotactic radiosurgery, but the results were poor. Two months after the fourth operation, she started treatment with temozolomide (200mg/m2, d1-5, 28d, orally) and apatinib (0.425g, daily, orally). Her GH level dropped to normal with a >90% decrease in tumor size, after 1-year treatment. There was no evidence of recurrence by imaging or by serum GH levels over 31.5 months of follow-up. CONCLUSION: we successfully treated this patient with recurrent invasive pituitary adenoma with temozolomide and apatinib for 31.5 months without recurrence. Angiogenesis is an active process in the cases of invasive pituitary adenomas that cannot be controlled by conventional therapy.