Nitrosoureas
Nitrosoureas
are
alkylating agents that work by halting cancer cell reproduction. They include:
• carmustine
• lomustine
• streptozocin.
When administered
topically to treat mycosis fungoides (a rare skin malignancy), carmustine is
5% to 28% systemically absorbed.After oral administration, lomustine is absorbed adequately,though
incompletely.
Streptozocin and
carmustine are administered I.V. because they’re poorly absorbed orally.
Nitrosoureas are
lipophilic (attracted to fat), distributing to fattytissues and cerebrospinal fluid.
They’re metabolized extensivelybefore urine excretion.
During a process called bifunctional alkylation, nitrosoureas in-terfere with amino acids,
purines, and DNA needed for cancer cells to divide, thus halting their
reproduction.
The nitrosoureas are highly lipid (fat) soluble,
which allows them or their metabolites to easily cross the blood-brain barrier.
Be-cause of this ability, nitrosoureas are used to treat brain tumors and
meningeal leukemias.
Each of the nitrosoureas has its own interactions
with other drugs. Cimetidine may increase carmustine’s bone marrow toxici-ty.
Streptozocin prolongs the elimination half-life of doxorubicin, prolonging the
leukopenia and thrombocytopenia. (See Adversereactions
to nitrosoureas.)
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