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Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide.

Bengtsson, Daniel; Daa Schrøder, Henrik; Andersen, Marianne; Maiter, Dominique; Berinder, Katarina; Feldt Rasmussen, Ulla; Krogh Rasmussen, Åse; Johannsson, Gudmundur; Hoybye, Charlotte and van der Lely, Aart Jan, et al. (2015) In Journal of Clinical Endocrinology and Metabolism 100(4). p.1689-1698
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/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, median 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-23% in LAPTs, and 5-90% in carcinomas. Main outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA... (More)
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/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, median 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-23% in LAPTs, and 5-90% 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 2 carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35-80% 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 non-responders. 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. (Less)
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published
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Journal of Clinical Endocrinology and Metabolism
volume
100
issue
4
pages
1689 - 1698
publisher
The Endocrine Society
external identifiers
  • pmid:25646794
  • wos:000353361500081
  • scopus:84927609324
ISSN
1945-7197
DOI
10.1210/jc.2014-4350
language
English
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yes
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4b082dbb-b963-4fc9-a182-3fa3601f69f9 (old id 5145580)
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http://www.ncbi.nlm.nih.gov/pubmed/25646794?dopt=Abstract
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2015-03-03 20:46:54
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2017-11-05 03:00:51
@article{4b082dbb-b963-4fc9-a182-3fa3601f69f9,
  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/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, median 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-23% in LAPTs, and 5-90% 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 2 carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35-80% 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 non-responders. 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.},
  author       = {Bengtsson, Daniel and Daa Schrøder, Henrik and Andersen, Marianne and Maiter, Dominique and Berinder, Katarina and Feldt Rasmussen, Ulla and Krogh Rasmussen, Åse and Johannsson, Gudmundur and Hoybye, Charlotte and van der Lely, Aart Jan and Petersson, Maria and Ragnarsson, Oskar and Burman, Pia},
  issn         = {1945-7197},
  language     = {eng},
  number       = {4},
  pages        = {1689--1698},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide.},
  url          = {http://dx.doi.org/10.1210/jc.2014-4350},
  volume       = {100},
  year         = {2015},
}