title: Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide.
abstract: OBJECTIVE
  Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited.
  
  
  METHODS
  We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas.
  
  
  RESULTS
  Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry.
  
  
  RESULTS
  Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ.
  
  
  CONCLUSIONS
  This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
authors: Department of Endocrinology (D.B., P.B.), Skane University Hospital, SE-205 02 Malmö, Sweden; Department of Pathology (H.D.S.), and Department of Endocrinology (M.A.), Odense University Hospital, University of Southern Denmark 5000 Odense, Denmark; Department of Endocrinology and Nutrition (D.M.), Cliniques Universitaires St-Luc, Université Catholique de Louvain, 1200 Brussels, Belgium; Department of Endocrinology, Metabolism and Diabetology (K.B., C.H., M.P.), Karolinska University Hospital, SE-141 86 Stockholm, Sweden; Department of Medical Endocrinology and Metabolism (U.F.R, Å.K.R), Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; Department of Medicine, Division of Endocrinology (A.J.v.d.L.), Erasmus University MC, 3000 CA Rotterdam, The Netherlands; and Department of Endocrinology (G.J., O.R.), Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors: Daniel
authors: D
authors: Bengtsson
authors: Henrik Daa
authors: HD
authors: Schrøder
authors: Marianne
authors: M
authors: Andersen
authors: Dominique
authors: D
authors: Maiter
authors: Katarina
authors: K
authors: Berinder
authors: Ulla
authors: U
authors: Feldt Rasmussen
authors: Åse Krogh
authors: ÅK
authors: Rasmussen
authors: Gudmundur
authors: G
authors: Johannsson
authors: Charlotte
authors: C
authors: Hoybye
authors: Aart Jan
authors: AJ
authors: van der Lely
authors: Maria
authors: M
authors: Petersson
authors: Oskar
authors: O
authors: Ragnarsson
authors: Pia
authors: P
authors: Burman
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide