title: Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment.
abstract: Pituitary carcinomas are rare, accounting for about 0.2% of all pituitary tumours. They represent a challenge to clinical practice in both diagnosis and treatment. They may present initially as typical pituitary adenomas, with a delayed appearance of aggressive signs, or as aggressive tumours from the outset. Predicting the pituitary tumour behaviour remains difficult: increased mitotic, Ki-67 and P53 indices might be associated with tumour aggression. The treatment of pituitary carcinomas and aggressive pituitary tumours includes surgery, adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Recent case reports have detailed the successful use of temozolomide, an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas and aggressive pituitary tumours. The outcome of treatment might depend on the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that potentially interferes with drug efficacy. This review describes the clinical presentation and response to temozolomide in 44 patients with pituitary carcinomas or aggressive pituitary tumours reported in the literature. The results suggest that temozolomide should be considered a drug of major importance in the therapeutic algorithm of aggressive pituitary tumours and pituitary carcinomas. Because of the inconsistency of published data, MGMT expression should probably not be taken as a reason to deny these patients the potential benefit of temozolomide treatment, taking into account the paucity of other available treatments.
authors.affiliation: INSERM, U1028, Faculté de Médecine Lyon-Est, Université de Lyon, Lyon1, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Raverot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Castinetti
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jouanneau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Morange
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Henry
authors.initials: H
authors.lastname: Dufour
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Trouillas
authors.forename: Thierry
authors.initials: T
authors.lastname: Brue
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide