Apatinib (YN968D1) and Temozolomide in Recurrent Invasive Pituitary Adenoma: Case Report and Literature Review

BACKGROUND: 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. CASE DESCRIPTION: 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(2), 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. CONCLUSIONS: 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.