Aggressive pituitary tumours: the role of temozolomide and the assessment of MGMT status
- 18 April 2011
- journal article
- Published by Wiley in European Journal of Clinical Investigation
- Vol. 41 (10), 1133-1148
- https://doi.org/10.1111/j.1365-2362.2011.02520.x
Abstract
BACKGROUND: Aggressive pituitary tumours are associated with substantial morbidity and mortality. Treatment options are often limited, and chemotherapy has been reserved as salvage therapy although historically results have often been disappointing. However, temozolomide, an oral alkylating agent, has recently demonstrated significant activity against these tumours. A DNA repair protein, 06-methylguanine-DNA methyltransferase (MGMT) has been suggested as a biomarker to predict response to temozolomide in pituitary tumours. MATERIALS AND METHODS: This paper will review the current literature on temozolomide and pituitary tumours and discuss the recent controversy surrounding the value of determining the MGMT status in this tumour group. A PubMed search was performed to retrieve articles, using the terms 'pituitary tumour' and 'temozolomide'. RESULTS: Overall, 24/40 (60%) of the published cases demonstrated a response to temozolomide therapy. The highest response rates were seen amongst prolactinomas (73%) and ACTH-secreting tumours (60%), whilst nonfunctioning pituitary tumours exhibit lower response rates (40%). Responsivity is typically evident in the first 3 months of therapy and may be dramatic and sustained. Low MGMT expression, as determined by immunohistochemistry, is associated with a high response rate (76%), whilst high MGMT expression has not been associated with responses. MGMT promoter methylation does not correlate with temozolomide response. CONCLUSIONS: Temozolomide is the first chemotherapeutic agent to show substantial response rates in aggressive pituitary tumours. MGMT immunohistochemistry, but not MGMT methylation analysis, shows promise as a predictive tool. Prospective clinical trials are now necessary to more accurately determine the efficacy of this agent in this patient groupKeywords
This publication has 70 references indexed in Scilit:
- Prevalence of pituitary adenomas: a community‐based, cross‐sectional study in Banbury (Oxfordshire, UK)Clinical Endocrinology, 2010
- A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumorsEndocrine-Related Cancer, 2007
- Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor RegistryActa Endocrinologica, 2007
- High Prevalence of Pituitary Adenomas: A Cross-Sectional Study in the Province of Liège, BelgiumJournal of Clinical Endocrinology & Metabolism, 2006
- Diagnosis and Management of Pituitary CarcinomasJournal of Clinical Endocrinology & Metabolism, 2005
- The Role of Cytotoxic Chemotherapy in the Management of Aggressive and Malignant Pituitary TumorsJournal of Clinical Endocrinology & Metabolism, 1998
- Pituitary carcinomaCancer, 1997
- Invasiveness of Pituitary AdenomasPathology - Research and Practice, 1991
- Pathology of invasive pituitary tumors with special reference to functional classificationJournal of Neurosurgery, 1986
- Primary Pituitary Carcinoma: A Clinical Pathological StudyNeurosurgery, 1985