title: Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.
abstract: 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.
authors.affiliation: Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge & Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Annamalai
authors.forename: A F
authors.initials: AF
authors.lastname: Dean
authors.forename: N
authors.initials: N
authors.lastname: Kandasamy
authors.forename: K
authors.initials: K
authors.lastname: Kovacs
authors.forename: H
authors.initials: H
authors.lastname: Burton
authors.forename: D J
authors.initials: DJ
authors.lastname: Halsall
authors.forename: A S
authors.initials: AS
authors.lastname: Shaw
authors.forename: N M
authors.initials: NM
authors.lastname: Antoun
authors.forename: H K
authors.initials: HK
authors.lastname: Cheow
authors.forename: R W
authors.initials: RW
authors.lastname: Kirollos
authors.forename: J D
authors.initials: JD
authors.lastname: Pickard
authors.forename: H L
authors.initials: HL
authors.lastname: Simpson
authors.forename: S J
authors.initials: SJ
authors.lastname: Jefferies
authors.forename: N G
authors.initials: NG
authors.lastname: Burnet
authors.forename: M
authors.initials: M
authors.lastname: Gurnell
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000473:pathology; D000236:Adenoma / Q000188:drug therapy; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
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