title: Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center.
abstract: Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150-200 mg/m(2) daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600-900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy, ceccato.filippo@gmail.com.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ceccato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuelli
authors.forename: Luca
authors.initials: L
authors.lastname: Denaro
authors.forename: Laura
authors.initials: L
authors.lastname: Milanese
authors.forename: Marina Paola
authors.initials: MP
authors.lastname: Gardiman
authors.forename: Roberta
authors.initials: R
authors.lastname: Bertorelle
authors.forename: Massimo
authors.initials: M
authors.lastname: Scanarini
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Avella
authors.forename: Gianluca
authors.initials: G
authors.lastname: Occhi
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D000077204:Temozolomide; D062606:Tertiary Care Centers
chemical_list: D018906:Antineoplastic Agents, Alkylating; D013004:Somatostatin; D003606:Dacarbazine; C517782:pasireotide; D000077204:Temozolomide