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

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.

• Authors: Daniel Bengtsson, 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
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 100 Issue 4 Pg. 1689-98 (Apr 2015) ISSN: 1945-7197 [Electronic] United States
• PMID: 25646794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Biomarkers, Pharmacological
• Biomarkers, Tumor
• Tumor Suppressor Proteins
• Dacarbazine
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes
• Temozolomide

Topics

• Adenoma (diagnosis, drug therapy, metabolism, pathology)
• Adolescent
• Adult
• Aged
• Antineoplastic Agents, Alkylating (therapeutic use)
• Biomarkers, Pharmacological (metabolism)
• Biomarkers, Tumor (metabolism)
• Carcinoma (diagnosis, drug therapy, metabolism, pathology)
• DNA Modification Methylases (metabolism)
• DNA Repair Enzymes (metabolism)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Female
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Pituitary Neoplasms (diagnosis, drug therapy, metabolism, pathology)
• Prognosis
• Temozolomide
• Treatment Outcome
• Tumor Suppressor Proteins (metabolism)
• Young Adult