semustine

Semustine, also known as methyl-CCNU, is a nitrosourea alkylating chemotherapeutic agent. It is lipophilic and orally active, enabling it to penetrate the blood–brain barrier and reach tumor tissue within the central nervous system. Like other nitrosoureas, semustine alkylates DNA by forming chloroethyl adducts that lead to cross-links and strand breaks, thereby inhibiting cell replication and inducing cell death. Its cytotoxic effects are greatest in rapidly dividing cells, but normal tissues with high turnover are also affected.

Semustine has been used in the treatment of brain tumors, including gliomas, and in certain regimens for hematologic malignancies such as lymphomas and leukemias. It is typically given by mouth in cyclical chemotherapy protocols, sometimes in combination with radiotherapy or other cytotoxic drugs. Its pharmacokinetic profile is characterized by relatively high tissue penetration and a long terminal half-life due to extensive binding and slow clearance; it is metabolized in the liver and eliminated by the kidneys.

The principal dose-limiting toxicity of semustine is myelosuppression, with neutropenia and thrombocytopenia commonly observed. Additional adverse effects include nausea and vomiting, mucositis, hepatic enzyme elevations or liver injury, renal dysfunction, pulmonary toxicity, and, like other alkylating agents, a risk of long-term secondary malignancies. Semustine is used selectively where benefits outweigh these risks, and its use has declined in some settings with the development of newer therapies.

See also: lomustine (CCNU), carmustine (BCNU), nitrosourea alkylating agents.