Carmustine (BCNU) is a parenterally administered alkylating agent used alone and in combination with other antineoplastic agents in the treatment of several forms of cancer including leukemias, lymphomas, and breast, testicular, ovarian, gastric and pancreatic cancer. Carmustine therapy is associated with minor transient serum enzyme elevations and has been linked to cases of acute liver injury including cholestatic hepatitis and acute veno-occlusive disease.


Carmustine (kar mus' teen), which is also known as BCNU, is a nitrosourea that acts as an alkylating agent and is used in the therapy of several forms of leukemia, lymphoma and solid organ cancer. Like cyclophosphamide, carmustine requires activation in the liver to form its active intermediates which act by modifying and cross linking purine bases in DNA, thus inhibiting DNA, RNA and protein synthesis and leading to cell death in rapidly dividing cells. Carmustine also forms adducts with intracellular proteins. Carmustine was approved for use in the United States in 1977, and its current uses include treatment of breast, gastric, liver, pancreatic, lung, brain, ovarian and testicular cancer, malignant melanoma, Hodgkin and non-Hodgkin lymphoma and multiple myeloma. 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. 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 onset of sinusoidal obstruction syndrome is usually within two to three weeks of the myeloablation and is characterized by a sudden onset of abdominal pain, weight gain, ascites, marked increase in serum aminotransferase levels (and LDH), and subsequent jaundice and hepatic dysfunction. The severity of sinusoidal obstruction syndrome varies from a transient, self-limited injury to acute liver failure. The diagnosis of sinusoidal obstruction syndrome is usually based on clinical features of tenderness and enlargement of the liver, weight gain, ascites and jaundice occurring within 3 weeks of chemotherapy. Liver biopsy is diagnostic but often contraindicated, because of severe thrombocytopenia after hematopoietic cell transplantation.

Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury, particularly when used for myeloablation).

Mechanism of Injury

Most instances of hepatotoxicity from carmustine appear dose related and probably due to direct cytotoxicity. The sinusoidal obstruction syndrome induced by alkylating agents is probably related to their toxic effect on sinusoidal cells in the liver, causing their necrosis and release into the sinusoids, with subsequent obstruction and obliteration of hepatic veins. Carmustine is extensively metabolized by the hepatic cytochrome P450 system.

Outcome and Management

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.

Drug Class: Antineoplastic Agents, Alkylating Agents



Carmustine – BiCNU, Gliadel®


Antineoplastic Agents, Alkylating Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 17 January 2017

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