Lomustine

In this article, we will discuss Lomustine (Indications). So, let’s get started.

Lomustine (CCNU) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1-(2-chloro-ethyl)-3­-cyclohexyl-1-nitrosourea. It is a yellow powder with the empirical formula of C9H16ClN3O2 and a molecular weight of 233.71. Lomustine is soluble in 10% ethanol (0.05 mg per mL) and in absolute alcohol (70 mg per mL). Lomustine is relatively insoluble in water (<0.05 mg per mL). It is relatively un-ionized at a physiological pH. Lomustine is available in 10 mg, 40 mg, and 100 mg capsules for oral administration.

Clinical Pharmacology

Although it is generally agreed that lomustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins. Lomustine may be given orally. Following oral administration of radioactive lomustine at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours. The serum half-life of the metabolites ranges from 16 hours to 2 days. Tissue levels are comparable to plasma levels at 15 minutes after intravenous administration. Because of the high lipid solubility and the relative lack of ionization at physiological pH, lomustine crosses the blood-brain barrier quite effectively. Levels of radioactivity in the CSF are 50% or greater than those measured concurrently in plasma.

Indications

Lomustine has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in the following:

Brain tumors—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures.

Hodgkin’s disease—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

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