The management of aggressive pituitary tumours is challenging. These tumours are typically resistant to standard medical therapy and progressive tumour growth occurs despite multiple operations and radiotherapy. Chemotherapy has been reserved as salvage therapy, although historically results are often disappointing. However temozolomide, an oral alkylating agent, has recently demonstrated significant activity against these tumours. Over the past 6 years, growing international experience with the use of temozolomide in aggressive pituitary tumours is reflected in more than 40 published cases. A review of these cases demonstrates a 60% response rate overall to temozolomide, with prolactinomas and ACTH-secreting tumours more likely to respond compared with nonfunctioning pituitary tumours1. A degree of publication bias towards reporting of successful outcomes may be overstating the effectiveness of temozolomide in the management of aggressive pituitary tumours.
O-6-Methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, directly removes the alkylating lesion induced by temozolomide. MGMT expression, as determined by immunohistochemistry, shows promise as a biomarker of response to temozolomide, although there is concern about its clinical utility1. In addition, low MGMT expression has been reported with increased frequency amongst more aggressive pituitary tumours2. This suggests that MGMT may play a role in pituitary tumorigenesis. Indeed, we have recently found a difference in the gene expression profiles between pituitary tumours with low and high MGMT expression.
Temozolomide is the first chemotherapeutic agent to show promising efficacy in the treatment of aggressive pituitary tumours, and clinical trials are needed. Pituitary tumour MGMT expression may serve both as a biomarker of response to temozolomide and a prognostic marker.
1. McCormack AI, Wass JA & Grossman AB. Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status. Eur J Clin Invest 2011 41 113348.
2. Salehi F, Scheithauer BW, Kovacs K, Horvath E, Syro LV, Sharma S, et al. O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemical expression in pituitary corticotroph adenomas. Neurosurgery 2012 70 49196.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details are unavailable.
05 - 09 May 2012
European Society of Endocrinology