Long-term outcome and MGMT as a predictive marker in 24 patients with atypical pituitary adenomas and pituitary carcinomas given treatment with temozolomide.
(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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https://lup.lub.lu.se/record/5145580
- author
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 100
- issue
- 4
- pages
- 1689 - 1698
- publisher
- Oxford University Press
- external identifiers
-
- pmid:25646794
- wos:000353361500081
- scopus:84927609324
- pmid:25646794
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2014-4350
- language
- English
- LU publication?
- yes
- id
- 4b082dbb-b963-4fc9-a182-3fa3601f69f9 (old id 5145580)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25646794?dopt=Abstract
- date added to LUP
- 2016-04-01 09:50:14
- date last changed
- 2024-04-06 18:35:24
@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 = {{Oxford University Press}},
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}},
doi = {{10.1210/jc.2014-4350}},
volume = {{100}},
year = {{2015}},
}