|Molar mass||214.05 g mol−1|
|Melting point||30 °C (86 °F; 303 K)|
|GHS signal word||DANGER|
|GHS hazard statements||H300, H350, H360|
|GHS precautionary statements||P301+310, P308+313|
|R-phrases||R45, R46, R60, R61, R28|
|S-phrases||S22, S36/37/39, S45|
|LD50||20 mg kg−1 (oral, rat)|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Carmustine or BCNU (bis-chloroethylnitrosourea) is a mustard gas-related β-chloro-nitrosourea compound used as an alkylating agent in chemotherapy. As a dialkylating agent, BCNU is able to form interstrand crosslinks in DNA, which prevents DNA replication and DNA transcription.
It has the appearance of an orange-yellow solid.
Carmustine for injection is marketed under the name BiCNU by Bristol-Myers Squibb. In India, carmustine is marketed under the name Carustine by Curacell Biotech.
It is used in the treatment of several types of brain cancer (including glioma, glioblastoma multiforme, medulloblastoma and astrocytoma), multiple myeloma and lymphoma (Hodgkin's and non-Hodgkin). BCNU is sometimes used in conjunction with alkyl guanine transferase (AGT) inhibitors, such as O6-benzylguanine. The AGT-inhibitors increase the efficacy of BCNU by inhibiting the Direct Reversal pathway of DNA repair, which will prevent formation of the interstrand crosslink between the N1 of guanine and the N3 of cytosine.
It is also used as part of a chemotherapeutic protocol in preparation for hematological stem cell transplantation, a type of bone marrow transplant, in order to reduce the white blood cell count in the recipient (patient). Use under this protocol, usually with Fludarabine and Melphalan, was coined by oncologists at the University of Texas MD Anderson Cancer Center.
|This section does not cite any references or sources. (December 2012)|
Bone marrow may take 6 weeks to recover function following treatment with carmustine. Weekly monitoring of platelet and white blood cell counts are recommended as a basis for patient-specific adjustments to dosage regimens. Bone marrow and pulmonary toxicities are a function of lifetime cumulative dose. Pulmonary toxicity characterized by pulmonary infiltrates and/or fibrosis (scarring of the lungs). Cases of fatal pulmonary toxicity have been reported. Delayed onset pulmonary fibrosis and myelosuppression may occur. Thrombocytopenia usually occurs about 4 weeks post administration. Leukopenia occurs approximately 5–6 weeks after administration. Cumulative myelosuppression, manifested by more depressed indices may occur. Anemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia. The occurrence of acute leukemia and bone marrow dysplasias have been reported in patients following long-term nitrosourea therapy.
Nausea and vomiting after IV administration are noted frequently. This usually occurs within 2 hours of administration. This is usually dose related. Prior administration of antiemetics is effective in diminishing and sometimes preventing these effects.
A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase and bilirubin levels, has been reported in a small percentage of patients. Renal abnormalities consisting of progressive azotemia, decrease in kidney size and renal failure have been reported in patients who received large cumulative doses after prolonged therapy. Kidney damage has also been reported occasionally in patients receiving lower total doses.
In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs, Gliadel, infused with carmustine can be used. They are implanted under the skull during a surgery called a craniotomy.
Dr.Henry Brem, head of neurosurgery at Johns Hopkins, has done extensive research on the use of therapeutic gliadel wafers. The wafer gets past the challenge imposed by the blood brain barrier.
On standing in water under various conditions, two main modes of degradation occur and these are rationalized as follows.
The nonnitrosated nitrogen of 1 supplies electrons for an intromolecular displacement of Cl to give intermediate imino ether 2 which collapses to isocyanate 4 and highly reactive 3 which latter fragments, ejecting nitrogen and capturing OH to produce acetaldehyde, after enolization.
In the second mode, a cyclic fragmentation process (5) leads to isocyanate and N-hydroxy-2-chloroethylazine which undergoes fragmentation, losing nitrogen and capturing OH (to give 2-chloroethanol) or NH3 (to give 2-chloroethylamine). As 2-chloroethylamine is a known source of aziridine, this substance has potential alkylating activity. Also, ejection of nitrogen from 4 to 6 leads to electron deficient species which react with nucleophiles. The isocyanate (4) also adds nucleophiles. Thus, it is not certain at this stage which of these is the most responsible agent for the bioactivity or whether the antitumor properties are a blend of these.
- "Carmustine - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Retrieved 11 April 2012.
- Ewend MG, Brem S, Gilbert M, et al. (June 2007). "Treatment of single brain metastasis with resection, intracavity carmustine polymer wafers, and radiation therapy is safe and provides excellent local control". Clin. Cancer Res. 13 (12): 3637–41. doi:10.1158/1078-0432.CCR-06-2095. PMID 17575228.
- Bestian, Herbert (1950). "Über einige Reaktionen des Äthylen-imins". Justus Liebigs Annalen der Chemie 566 (2): 210–244. doi:10.1002/jlac.19505660210.
- Johnston, Thomas P. (1963). "The Synthesis of Antineoplastic Agents. XXXII. N-Nitrosoureas. 1 I.". Journal of Medicinal Chemistry 6 (6): 669–681. doi:10.1021/jm00342a010.