This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Related articles in The Oncologist Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agarwala, S. S. Articles by Kirkwood, J. M. Search for Related Content PubMed PubMed Citation Articles by Agarwala, S. S. Articles by Kirkwood, J. M.

Temozolomide, a Novel Alkylating Agent with Activity in the Central Nervous System, May Improve the Treatment of Advanced Metastatic Melanoma

University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

Correspondence: Sanjiv S. Agarwala, M.D., Associate Director, Melanoma Center, University of Pittsburgh Cancer Institute, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA. Telephone: 412-648-6507; Fax: 412-648-6579; e-mail: agarwalass{at}msx.upmc.edu

Abstract

Temozolomide (TMZ) is the first new chemotherapy agent to be approved for the treatment of high-grade malignant gliomas in more than 20 years. This novel oral alkylating agent has demonstrated promising activity not only in brain tumors, but in a variety of solid tumors, including malignant melanoma. TMZ is 100% bioavailable when taken orally and, because of its small size and lipophilic properties, it is able to cross the blood-brain barrier. Concentrations in the central nervous system are approximately 30% of plasma concentrations. Once it has entered the central nervous system, TMZ can be spontaneously converted to the active metabolite. These pharmacologic properties make it an ideal agent for treating central nervous system malignancies. In patients with advanced metastatic melanoma, brain metastases are a major cause of treatment failure. In this setting, TMZ has been shown to be as effective as dacarbazine, with a similar safety profile. More importantly, there is evidence to suggest that TMZ-treated patients have a lower incidence of central nervous system relapse compared with dacarbazine-treated patients. Therefore, TMZ is actively being investigated for the treatment and prevention of brain metastases in melanoma patients. TMZ may become an important part of treatment regimens for advanced metastatic melanoma.

Key Words. Antineoplastic agents • Alkylating • Central nervous system • Drug therapy • Imidazoles • Melanoma • Neoplasm metastasis • Pharmacokinetics

Related articles in The Oncologist:

New Drugs for Cancer: Temozolomide

Bruce A. Chabner
The Oncologist 2000 5: 0-1. [Full Text]  

This article has been cited by other articles:

				V. A. Trinh Current management of metastatic melanoma Am. J. Health Syst. Pharm., December 15, 2008; 65(24_Supplement_9): S3 - S8. [Abstract] [Full Text] [PDF]

				G. A. Geiger, W. Fu, and G. D. Kao Temozolomide-Mediated Radiosensitization of Human Glioma Cells in a Zebrafish Embryonic System Cancer Res., May 1, 2008; 68(9): 3396 - 3404. [Abstract] [Full Text] [PDF]

				W.-J. Hwu, S. E. Krown, K. S. Panageas, J. H. Menell, P. B. Chapman, P. O. Livingston, L. J. Williams, C. J. Quinn, and A. N. Houghton Temozolomide Plus Thalidomide in Patients With Advanced Melanoma: Results of a Dose-Finding Trial J. Clin. Oncol., June 1, 2002; 20(11): 2610 - 2615. [Abstract] [Full Text] [PDF]

				B. A. Chabner New Drugs for Cancer: Temozolomide Oncologist, April 1, 2000; 5(2): 0 - 1. [Full Text] [PDF]