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Oncology Treatment of Aggressive Pituitary Adenomas and Carcinomas – An Overview Luis V Syro, 1 Leon D Ortiz, 2 Fabio Rotondo, 3 Humberto Uribe, 4 Luis C Penagos, 5 Eva Horvath 6 and Kalman Kovacs 7 1. Neurosurgeon, Department of Neurosurgery, Pablo Tobón Uribe Hospital and Medellin Clinic, Medellin, Colombia; 2. Neuro-oncologist, Division of Neuro-oncology, Cancerology Institute, Las Americas Clinic, Medellin, Colombia; 3. Research Associate, Department of Laboratory Medicine, Division of Pathology, St Michael’s Hospital, University of Toronto, Ontario, Canada; 4. Professor, Department of Neurosurgery, SOMA Clinic, Medellin, Colombia; 5. Professor, Division of Otolaryngology, Medellin Clinic, Medellin, Colombia; 6. Senior Scientist, Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Ontario, Canada; 7. Emeritus Professor, Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, University of Toronto, Ontario, Canada Abstract Most pituitary tumours are non-invasive, benign adenomas that remain confined to the sella turcica. Some of them recur, have a rapid growth rate, and invade surrounding tissues. These adenomas, considered aggressive pituitary tumours, are difficult to manage and present problems due to incomplete resection. A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented. Treatment options for pituitary adenomas are surgery, radiation and drugs. Recent publications report the efficacy of temozolomide in the treatment of aggressive pituitary adenomas and carcinomas. Indications for, results with, and side effects of temozolomide therapy in aggressive pituitary tumours and pituitary carcinomas are reviewed here. Alternative treatment options for resistant or recurrent pituitary tumours are also discussed. Keywords Pituitary adenoma, pituitary carcinoma, O 6 -methylguanine-DNA methyltransferase (MGMT), temozolomide, everolimus, bevacizumab Disclosure: The authors have no conflicts of interest to declare. Acknowledgements: The authors are grateful to the Jarislowsky and Lloyd Carr-Harris Foundations for their continuous support. Received: 4 June 2012 Accepted: 19 June 2012 Citation: European Neurological Review, 2012;7(3):178–80 Correspondence: Luis V Syro, Department of Neurosurgery, Hospital Pablo Tobón Uribe and Clinica Medellin, Calle 54 # 46-27, Cons 501, Medellin, Colombia. E: lvsyro@une.net.co Most pituitary tumours are non-invasive, benign adenomas that remain confined to the sella turcica. Although there is, at present, no accepted definition of aggressive pituitary adenomas, one would suggest that these have a tendency to recur after initial surgery. They have a rapid growth rate and invade surrounding structures such as the sphenoid and cavernous sinus as well as the skull base bone. They are clinically difficult to manage and present major problems due to incomplete resection. 1 was variable; approximately 75 % of patients with systemic metastasis died of the disease within one year. 4 Recent publications report efficacy of temozolomide, an alkylating agent used to treat gliomas, in the management of aggressive pituitary adenomas and carcinomas. 6–36 As in gliomas, the outcome of treatment might depend on the expression of O 6 -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that counteracts the action of temozolomide. 6,13,37 Temozolomide Pituitary carcinomas are rare – 0.2  % of all pituitary tumours. They present major diagnostic and therapeutic challenges. They may initially appear as benign pituitary adenomas subsequently transforming into an aggressive neoplasm, or they may be aggressive tumours from the beginning. 2–4 A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented. 5 Predicting pituitary tumour behaviour remains a real challenge. Studies suggest that increased mitotic activity, high Ki-67, nuclear labelling index and P53 expression might be associated with tumour progression. 3,5 Temozolomide is an alkylating chemotherapeutic agent related to a series of imidazotetrazines. Orally administered, it readily crosses the blood–brain barrier. It exerts its cytotoxic effect through methylation of DNA at the O 6 position of guanine, 38 which then mispairs with thymine during the next cycle of DNA replication. Temozolomide is accepted as an effective drug in the treatment of glioblastoma multiforme and other tumours of the central nervous system. 39 Recent reports point out its efficacy in malignant neuroendocrine neoplasms, 40 melanomas 41,42 and colorectal carcinomas. 43 Multiple treatment approaches – including surgery, external beam radiotherapy, gamma knife, drugs and various chemotherapeutic agents – have been used. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Progression of disease after a diagnosis of pituitary carcinoma The standard therapeutic dose of temozolomide is 150–200 mg/m 2 on Days 1–5 of a 28-day cycle (5/28). Depletion of MGMT has been proposed as a means of tumour response to temozolomide. 44 Experimental and clinical data have shown that response to temozolomide is schedule-dependent and that alternative dosing 178 © TOUCH BRIEFINGS 2012