Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide

• Published in: The journal of clinical endocrinology and metabolism Vol. 100; no. 4; pp. 1689 - 1698
• Main Authors: Bengtsson, Daniel, Schrøder, Henrik Daa, Andersen, Marianne, Maiter, Dominique, Berinder, Katarina, Feldt Rasmussen, Ulla, Rasmussen, Åse Krogh, Johannsson, Gudmundur, Hoybye, Charlotte, van der Lely, Aart Jan, Petersson, Maria, Ragnarsson, Oskar, Burman, Pia
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.04.2015; Copyright by The Endocrine Society
• Subjects: Adenoma - diagnosis; Adenoma - drug therapy; Adenoma - metabolism; Adenoma - pathology; Adolescent; Adult; Aged; Antineoplastic Agents, Alkylating - therapeutic use; Biomarkers, Pharmacological - metabolism; Biomarkers, Tumor - metabolism; Carcinoma - diagnosis; Carcinoma - drug therapy; Carcinoma - metabolism; Carcinoma - pathology; Clinical Medicine; Dacarbazine - analogs & derivatives; Dacarbazine - therapeutic use; DNA Modification Methylases - metabolism; DNA Repair Enzymes - metabolism; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; EXPERIENCE; Female; Follow-Up Studies; GLIOBLASTOMA; Humans; Klinisk medicin; Male; MALIGNANT GLIOMA; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; O-6-METHYLGUANINE DNA METHYLTRANSFERASE; OF-THE-LITERATURE; Pituitary Neoplasms - diagnosis; Pituitary Neoplasms - drug therapy; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Prognosis; PROMOTER METHYLATION; REPAIR PROTEIN MSH6; RESISTANT; THERAPY; Treatment Outcome; Tumor Suppressor Proteins - metabolism; TUMORS; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2014-4350

Context/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. Design and Setting: 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. Main Outcome: 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.