title: Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.
abstract: BACKGROUND
  To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide.
  
  
  OBJECTIVE
  The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression.
  
  
  METHODS
  Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study.
  
  
  METHODS
  MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing.
  
  
  RESULTS
  Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients.
  
  
  CONCLUSIONS
  Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 842, Université de Lyon, Faculté de Médecine Lyon-Est, Lyon, France. gerald.raverot@chu-lyon.fr
authors.forename: Gérald
authors.initials: G
authors.lastname: Raverot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.forename: Florence
authors.initials: F
authors.lastname: de Fraipont
authors.forename: Marie
authors.initials: M
authors.lastname: Muller
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Philippe
authors.initials: P
authors.lastname: Caron
authors.forename: Olivier
authors.initials: O
authors.lastname: Chabre
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
authors.forename: Christine
authors.initials: C
authors.lastname: Cortet-Rudelli
authors.forename: Richard
authors.initials: R
authors.lastname: Assaker
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.forename: Stephan
authors.initials: S
authors.lastname: Gaillard
authors.forename: Patrick
authors.initials: P
authors.lastname: François
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jouanneau
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Passagia
authors.forename: Michèle
authors.initials: M
authors.lastname: Bernier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cornélius
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015175:Prolactinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide