Nitrosourea

Nitrosoureas belong to the group of alkylants. Like the nitrogen-lost derivatives, they contain chloroethyl radicals as well as a highly reactive nitroso group. The substances decompose spontaneously and release the alkylating ethyl carbonium ion, which causes cross-linking of the DNA by alkylation of guanine and cytosine. In addition, isocyanates are formed, which also inhibit DNA repair by combining with the DNA polymerase. Nitrosourea derivatives have a non-phase-specific effect, i.e. they also act on resting cells.

Many nitrosoureas are able to cross the blood-brain barrier due to their small molecule size and lipophilicity. They are therefore suitable for the treatment of CNS metastases and brain tumours.

• Carmustine (BCNU) 1,3-Bis(2-chloroethyl)-1-nitrosourea
• Lomustine (CCNU) 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea
• Semustine N-(2-chloroethyl)-N′-(4-methylcyclohexyl)-N-nitrosourea
• Nimustin 1-[(4-amino-2-methylpyrimidin-5-yl) methyl]-3-(2-chloroethyl)-3-nitrosourea
• Streptozocin 2-deoxy-2-(3-methyl-3-nitroso-ureido)-D-glucopyranose
• Fotemustine 1-(2-chloroethyl)-3-(1-diethoxyphosphorylethyl)-1-nitrosourea

Nitrosoureas are highly myelotoxic with a particular effect on blood formation, especially of the thrombocytes and leucocytes. The number of thrombocytes and leukocytes decreases with a significant delay, from about 4 to 6 weeks after the start of therapy. For this reason, the intervals between two treatment cycles must be longer for nitrosourea than for other cytostatic agents.

Further side effects are to be expected on the gastrointestinal tract (nausea, vomiting). In addition, hair loss as well as kidney, liver (Lomustin) and lung toxicity (Carmustin) are also expected.

The nitrosoureas are carcinogenic. High-dose therapies can induce bladder cancer.