Daniel Bengtsson1, Henrik Daa Schrøder, Marianne Andersen, Dominique Maiter, Katarina Berinder, Ulla Feldt Rasmussen, Åse Krogh Rasmussen, Gudmundur Johannsson, Charlotte Hoybye, Aart Jan van der Lely, Maria Petersson, Oskar Ragnarsson, Pia Burman. 1. 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.
Abstract
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.
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 tumoralMGMT staining below 50% is associated with a high likelihood of treatment response.
Authors: P D Delgado-López; J Pi-Barrio; M T Dueñas-Polo; M Pascual-Llorente; M C Gordón-Bolaños Journal: Clin Transl Oncol Date: 2018-04-05 Impact factor: 3.405