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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

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