Bone marrow depression carmustine

The main drugs in this group are lomustine, carmustine, semustine and streptozotocin. The nitrosoureas are lipophilic and cross the blood-brain barrier. They are therefore effective against brain tumours. They cause a severe cumulative bone marrow depression that starts within 1-2 months of treatment. Lomustine and carmustine cause direct injury to the pulmonary epithelium leading to alveolar fibrosis. Streptozotocin has little bone marrow toxicity, but destroys the pancreatic 3 cells, causing diabetes mellitus. 

Carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNU) generate alkyl car-bonium ions and isocyanate molecules and hence are able to interact with DNA and other macromolecules. These agents, which are lipid soluble, cross the blood-brain barrier and are therefore effective in treating brain tumors. They are bone marrow depressants. 

Of 91 patients treated with topical carmustine, three developed reversible bone marrow depression (13). 

Selker RG, Moore P, Lodolce D. Bone-marrow depression with cimetidine plus carmustine. N Engl J Med 1978 299(15) 834. 

The bone marrow depressant effects of carmustine and lomustine are possibly increased by cimetidine. 

Nine patients treated with carmustine 80 mg/m daily for 3 days, cimetidine 300 mg four times daily for 1 to 4 weeks, steroids, and cranial irradiation over 6 weeks, demonstrated marked leucopenia during the first cycle. Bone marrow aspirates confirmed the marked decrease in granulocytic elements in 2 patients. In comparison, 31 patients treated similarly, but without cimetidine, had no significant white cell depression. Neutropenia was found in a man taking regular cimetidine, phenytoin, phenobarbital, and dexamethasone, 53 days after he was given lomustine 120 mg, and 16 days after he was given lomustine 160 mg. The cimetidine was discontinued and the neutropenia rapidly reversed within 14 days. The neutrophil nadir from the lomustine 160 mg dose occurred after a further 16 to 19 days and was much less severe. ... 

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