LAUSR

Abstract Introduction: Aggressive corticotroph tumors exhibit continued growth despite multimodal therapy, including surgeries, radiotherapy and/or medical treatment. Temozolomide (TMZ), an oral alkylating agent, has been used to treat aggressive pituitary tumors; however, most patients only showed a partial response. Recent evidence suggests that TMZ administered with capecitabine (CAP) is effective and safe in treating patients with aggressive corticotroph tumors resistant to conventional therapy. Here, we present two patients with recurrence of aggressive corticotroph pituitary tumors after surgery and radiation therapy and good response to treatment with CAP and TMZ (CAPTEM). Clinical presentation: Case 1: A 54-year-old man presented with right-sided headache and dizziness. Examination revealed palsies of the right 3rd, 4th, 5th and 6th cranial nerves. MRI confirmed a 3.6 x 3.7 x 3.5 cm sellar/suprasellar mass with right cavernous sinus invasion, chiasmal compression and clival replacement. He had transsphenoidal surgery and pathology showed a sparsely granulated ACTH adenoma with necrosis. With evidence of hypopituitarism, he was placed on prednisone, levothyroxine and testosterone. He also received stereotactic radiotherapy to manage his residual adenoma. Three years later, he presented with new onset neck pain and imaging studies showed leptomeningeal disease and biopsy confirmed ACTH adenoma. He was treated with CAPTEM for one year which resulted in clinical remission with marked radiological improvement, and persistent tumor control 20 months after cessation of therapy. Case 2: A 48 year-old man seen post transsphenoidal surgery for management of his recurrent silent corticotroph adenoma. He presented at age 21 with vision loss and had his first craniotomy. At age 31, he had repeat craniotomy for tumor recurrence that was followed by radiation therapy. With documented hypopituitarism, he has been on hydrocortisone, levothyroxine and testosterone. Although he has been legally blind, he did notice further vision loss prior to his transsphenoidal surgery. MR sella showed a 3.0 x 3.6 x 2.5 cm sellar mass infiltrating the clivus, sphenoid sinus, both cavernous sinuses and extending and compressing the optic chiasm. Even though there was good debulkment of the sellar mass, rapid tumor regrowth was noted on follow up MRI 18 months later. As the neurosurgeon did not feel that the patient would benefit from further surgery, he was treated with a year of CAPTEM. This led to significant tumor shrinkage with no tumor regrowth four months after completion of therapy. Conclusion: Our cases represent the sixth and seventh cases of CAPTEM-treated aggressive corticotroph tumors with good response to therapy. TMZ in combination with CAP seems to be promising in the management of patients with aggressive corticotroph pituitary tumors, and potentially other aggressive pituitary adenomas.