Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.

Abstract

e13022 Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were >200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.