Wang Yong, He Qiaowei, Meng Xiangji, Zhou Shizhen, Zhu Yufang, Xu Jun, Tao Rongjie
Department of Neurosurgery, Shandong Cancer Hospital Affiliated with Shandong University, Shandong Academy of Medical Sciences, Jinan, China.
Department of Neurosurgery, Qingdao University Affiliated with Yantai Yuhuangding Hospital, Yantai, China.
World Neurosurg. 2019 Apr;124:319-322. doi: 10.1016/j.wneu.2018.12.174. Epub 2019 Jan 11.
Invasive pituitary adenomas often recurred after postoperative radiotherapy and are difficult to treat. Temozolomide 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 an 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.
We present a 41-year-old female with a growth hormone (GH)-secreting invasive pituitary adenoma causing menstrual disorder and headache symptoms. Over 3 years, she underwent 4 surgeries and a stereotactic radiosurgery, but the results were poor. Two months after the fourth operation, she started treatment with temozolomide (200 mg/m, days 1-5, 28 days, orally) and apatinib (0.425 g, 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.
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.
侵袭性垂体腺瘤术后放疗后常复发，且难以治疗。替莫唑胺是一种烷化剂类细胞抑制剂，据报道可减小垂体肿瘤大小并减少激素分泌过多。然而，这还远远不够。垂体腺瘤中血管内皮生长因子表达相对较高。因此，抗血管生成药物已被用于少数复发后的侵袭性或恶性垂体肿瘤。阿帕替尼（YN968D1）是一种小分子抗血管生成药物，可选择性抑制血管内皮生长因子受体-2（VEGFR-2），还可轻度抑制在侵袭性垂体腺瘤中大量存在的c-Kit和c-Src酪氨酸激酶。
我们报告一名41岁女性，患有分泌生长激素（GH）的侵袭性垂体腺瘤，导致月经紊乱和头痛症状。3年多来，她接受了4次手术和1次立体定向放射外科治疗，但效果不佳。第四次手术后两个月，她开始接受替莫唑胺（200 mg/m²，第1 - 5天，每28天口服一次）和阿帕替尼（0.425 g，每日口服）治疗。经过1年治疗，她的GH水平降至正常，肿瘤大小减小超过90%。在31.5个月的随访中，影像学检查或血清GH水平均未发现复发迹象。
我们成功地用替莫唑胺和阿帕替尼治疗了这名复发性侵袭性垂体腺瘤患者31.5个月，无复发。血管生成在侵袭性垂体腺瘤病例中是一个常规治疗无法控制的活跃过程。
