On Mar. 7, 1977, the U.S. Food and Drug Administration approved Bristol-Myers’ BICNU (carmustine), for the treatment of brain and lymphatic cancers. BiCNU is a nitrosourea indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents.

Carmustine is given intravenously and is available in liquid formulations (100 mg vials) in generic forms and under the trade names Gliadel or BiCNU. Recommended doses vary by age, body weight and malignant condition.

Carmustine is often given in combination with other antineoplastic agents or alone in cycles every 6 to 8 weeks. It is also available formulated in a wafer containing 7.7 mg of carmustine (Gliadel), which can be inserted in a surgical space such as the brain after resection of a high grade malignant glioma. The toxicity of carmustine is similar to other alkylating agents.

Mild and transient elevations in serum aminotransferase levels are found in up to 25% of patients treated with carmustine. Because carmustine is typically given in combination with other agents, its role in causing these serum enzyme elevations is not always clear. The abnormalities are generally transient, do not cause symptoms and do not require dose modification.

Clinically apparent liver injury from carmustine has been limited to a small number of cases of cholestatic hepatitis and more frequent instances of sinusoidal obstruction syndrome, reported mostly with its use in high doses or as a conditioning agent in preparation for hematopoietic cell transplantation. Common side effects include alopecia, nausea, vomiting, diarrhea, gastrointestinal upset, nephrotoxicity, oral ulcers and bone marrow suppression.

Mild and transient elevations in serum aminotransferase levels are found in up to 25% of patients treated with carmustine. Because carmustine is typically given in combination with other agents, its role in causing these serum enzyme elevations is not always clear. The abnormalities are generally transient, do not cause symptoms and do not require dose modification. Clinically apparent liver injury from carmustine has been limited to a small number of cases of cholestatic hepatitis and more frequent instances of sinusoidal obstruction syndrome, reported mostly with its use in high doses or as a conditioning agent in preparation for hematopoietic cell transplantation.

The severity of liver injury from carmustine ranges from mild elevations in liver enzymes, to a self limited cholestatic hepatitis to massive, fatal hepatic necrosis due to sinusoidal obstruction syndrome. There is currently no specific therapy for veno-occlusive disease other than supportive management and avoidance of further damage. Rechallenge should be avoided.