HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Temozolomide treatment for aggressive pituitary tumors: correlation of clinical outcome with O(6)-methylguanine methyltransferase (MGMT) promoter methylation and expression.

AbstractCONTEXT:
The typically indolent behavior of pituitary tumors is juxtaposed with high rates of tumor cell invasion into adjacent dural structures, and occasional aggressive behavior. Although clinically significant invasion and malignant transformation remain uncommon, there are limited treatment options available for the management of these aggressive tumors. Recently, case reports have described efficacy of temozolomide for the treatment of aggressive pituitary tumors.
DESIGN:
Seven patients with aggressive pituitary tumors have been treated with temozolomide. We compared O(6)-methylguanine methyltransferase (MGMT) promoter methylation and MGMT expression in 14 surgical specimens from these seven patients and correlated these molecular features with the clinical response to temozolomide.
RESULTS:
Significant tumor regression was seen in two patients (29%), a 20% reduction in tumor volume with subsequent stable tumor size was noted in one patient, arrest of tumor growth occurred in three patients, and progressive metastatic disease developed during treatment in one patient. The DNA promoter site for MGMT was unmethylated in all 14 adequate specimens, and variable MGMT expression was seen in all 14 cases. There was no correlation between MGMT expression and clinical outcomes.
CONCLUSIONS:
We conclude that medical therapy with temozolomide can be helpful in the management of life-threatening pituitary tumors that have failed to respond to conventional treatments. The optimal duration of treatment in patients with stabilization or reduction of tumor size has not been established, and long-term follow up studies are needed.
AuthorsZachary M Bush, Janina A Longtine, Tracy Cunningham, David Schiff, John A Jane Jr, Mary Lee Vance, Michael O Thorner, Edward R Laws Jr, M Beatriz S Lopes
JournalThe Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 95 Issue 11 Pg. E280-90 (Nov 2010) ISSN: 1945-7197 [Electronic] United States
PMID20668043 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents
  • Dacarbazine
  • O(6)-Methylguanine-DNA Methyltransferase
  • Temozolomide
Topics
  • Antineoplastic Agents (therapeutic use)
  • DNA Methylation
  • Dacarbazine (analogs & derivatives, therapeutic use)
  • Humans
  • Immunohistochemistry
  • O(6)-Methylguanine-DNA Methyltransferase (genetics, metabolism)
  • Pituitary Neoplasms (drug therapy, genetics, metabolism)
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Temozolomide
  • Treatment Outcome

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: