Brain metastases commonly occur in patients with metastatic melanoma and are associated with a poor prognosis. Only a few chemotherapeutic agents have been shown to be potentially active. Resistance to chemotherapy is one of the main limitations to treatment. A key mechanism of resistance is O6-methylguanine-DNA methyltransferase (MGMT). The methylation of its promotor could inhibit the activity of this enzyme; consequently, it is very important to evaluate the methylation status of all available specimens.
Case Report:
We report the case of a long-surviving patient in whom combination treatment with an alkylating agent inhibiting MGMT, such as temozolomide, was useful in clinical control of the disease.
Get full access to this article
View all access options for this article.
References
1.
NaumannSCRoosWPJöstE. Temozolomide- and fotemustine-induced apoptosis in human malignant melanoma cells: Response related to MGMT, MMR, DSBs, and p53. Br J Cancer2009;100:322–33, doi:10.1038/sj.bjc.6604856.
2.
MitchellRBDolanME. Effect of temozolomide and dacarbazine on O6-alkylguanine-DNA alkyltransferase activity and sensitivity of human tumor cells and xenografts to 1,3-bis(2-chloro-ethyl)-l-nitrosourea. Cancer Chemother Pharmacol1993;32:59–63, doi: 10.1007/BF00685877.
3.
PeggAE. Repair of O6-alkylguanine by alkyltransferases. Mutat Res2000;462:83–100, doi:10.1016/S1383-5742(00)00017-X.
4.
LeeSMThatcherNCrowtherDMargisonGP. Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. Br J Cancer1994;69:452–6, doi:10.1038/bjc.1994.82.
5.
ZakrzewskiJGeraghtyLNRoseAE. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastasis and post-brain metastasis survival. Cancer2011;117:1711–20, doi:10.1002/cncr.25643.
6.
SloanAENockCJEinsteinDB. Diagnosis and treatment of melanoma brain metastasis: A literature review. Cancer Control2009;16:248–55.
7.
BottoniUIzzoPRichettaA. S100 serum level: A tumour marker for metastatic melanoma. Melanoma Res2003;13:427–9, doi:10.1097/00008390-200308000-00014.
8.
TasFCamlicaHTopuzE. Temozolomide in combination with fotemustine in patients with metastatic melanoma. Cancer Chemother Pharmacol2008;62:293–8, doi:10.1007/s00280-007-0606-5.
9.
De RossiARossiLLaudisiA. Focus on fotemustine. J Exp Clin Cancer Res2006;25:461–8.
10.
GuidaMCramarossaAFistolaE. High activity of sequential low dose chemo-modulating temozolomide in combination with fotemustine in metastatic melanoma. A feasibility study. J Transl Med2010;8, 115, doi:10.1186/1479-5876-8-115.
11.
Di GiacomoAMAsciertoPAPillaL. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): An open-label, single-arm phase 2 trial. Lancet Oncol2012;13:879–86, doi:10.1016/S1470-2045(12)70324-8.
12.
MenaaF. Latest approved therapies for metastatic melanoma: What comes next?J Skin Cancer2013;2013, 735282, doi:10.1155/2013/735282. [Epub 2013 Feb 24]
13.
BatusMWaheedSRubyC. Optimal management of metastatic melanoma: Current strategies and future directions. Am J Clin Dermatol2013 May 16. [Epub ahead of print]
14.
JohnsonDBSosmanJA. Update on the targeted therapy of melanoma. Curr Treat Options Oncol2013;14:280–92, doi:10. 1007/s11864-013-0226-8.
