Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard
chemotherapy regimens showing limited efficacy. Recent evidence suggests that
temozolomide (TMZ), an orally-active
alkylating agent used principally in the management of
glioblastoma, may also be effective in controlling aggressive/invasive
pituitary adenomas/
carcinomas. A low level of expression of the
DNA-repair enzyme O6-methylguanine-DNA
methyltransferase (MGMT) predicts TMZ responsiveness in
glioblastomas, and a similar correlation has been observed in the majority of aggressive
pituitary adenomas/
carcinomas reported to date. Here, we report a case of a silent pituitary
corticotroph adenoma, which subsequently re-presented with
Cushing's syndrome due to functioning hepatic
metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ
therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in
adrenocorticotrophic hormone (
ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral
adrenalectomy. However, despite reintroduction of TMZ
therapy (further eight cycles)
ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary
neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ
therapy in
glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of
pituitary adenomas/
carcinomas are also considered.