Carmustine — Drug Monograph
Brand names: BiCNU, Gliadel
Drug class: Alkylating Agent
Mechanism of Action
Carmustine is a nitrosourea derivative that acts as a cell-cycle non-specific alkylating agent. It undergoes spontaneous hydrolysis to form reactive electrophilic carbonium ions that cause DNA cross-linking (both interstrand and intrastrand) and carbamoylation of proteins, particularly lysine residues. These actions inhibit DNA, RNA, and protein synthesis, eventually leading to apoptosis. Its high lipophilicity allows it to readily cross the blood-brain barrier, making it effective for central nervous system malignancies.
FDA Indications
- Brain tumors (glioblastoma, brainstem glioma, medulloblastoma, astrocytoma, ependymoma, and metastatic brain tumors)
- Multiple myeloma (in combination with prednisone)
- Relapsed or refractory Hodgkin’s lymphoma (in combination with other approved drugs)
- Relapsed or refractory Non-Hodgkin’s lymphomas (in combination with other approved drugs)
- Newly-diagnosed high-grade malignant glioma as an adjunct to surgery and radiation (Gliadel wafer)
- Recurrent glioblastoma multiforme as an adjunct to surgery (Gliadel wafer)
Common Side Effects
- Nausea
- Vomiting
- Myelosuppression (thrombocytopenia and leukopenia)
- Infusion site reactions
- Flushing
- Hypotension
- Increased liver enzymes
Clinical Pearl
The hallmark of carmustine toxicity is its delayed and cumulative myelosuppression, with nadirs often not reached for 4 to 6 weeks, requiring extended intervals between cycles. Clinicians must be vigilant about lifetime cumulative doses to minimize the risk of irreversible pulmonary fibrosis. For IV administration, the use of alcohol as a diluent can cause a "drunk" sensation or flushing, so patients should be monitored for infusion-related hypotension. The Gliadel wafer form requires careful…
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