Carmustine

Carmustine
Preferred IUPAC name N,N’-Bis(2-chloroethyl)-N-nitroso-urea[citation needed]
Systematic name 1,3-Bis(2-chloroethyl)-1-nitrosourea
Identifiers
CAS number	154-93-8 Y
PubChem	2578
ChemSpider	2480 Y
UNII	U68WG3173Y Y
EC number	205-838-2
UN number	2811
DrugBank	DB00262
KEGG	D00254 N
MeSH	Carmustine
ChEBI	CHEBI:3423 Y
ChEMBL	CHEMBL513 Y
RTECS number	YS2625000
ATC code	L01AD01
Jmol-3D images	Image 1 Image 2
SMILES ClCC[nH]:c(:[o]):n(CCCl):n:[o] ClCCNC(=O)N(CCCl)N=O
InChI InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11) Y Key: DLGOEMSEDOSKAD-UHFFFAOYSA-N Y
Properties
Molecular formula	C5H9Cl2N3O2
Molar mass	214.05 g mol−1
Exact mass	213.007181961 g mol−1
Appearance	Orange crystals
Odor	Odourless
Melting point	30 °C, 303 K, 86 °F
log P	1.375
Acidity (pKa)	10.194
Basicity (pKb)	3.803
Pharmacology
Bioavailability	5–28%
Routes of administration	Intravenous Intralesional
Metabolism	Hepatic
Elimination half-life	15–30 min
Protein binding	80%
Excretion	Renal Respiratory
Legal status	℞ Prescription only
Pregnancy category	D(US)
Hazards
GHS pictograms
GHS signal word	DANGER
GHS hazard statements	H300, H350, H360
GHS precautionary statements	P301+310, P308+313
EU classification	T+
R-phrases	R45, R46, R60, R61, R28
S-phrases	S22, S36/37/39, S45
LD50	20 mg kg−1 (oral, rat)
Related compounds
Related ureas	Dimethylurea
Related compounds	Noxytiolin 1,1,3,3-Tetramethylguanidine Metformin Buformin
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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.

Uses

Interstrand crosslink reaction between guanine and cytosine after monoadduct formation.

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.

Side effects

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

Pulmonary toxicity characterised by pulmonary infiltrates and/or fibrosis (scarring of the lungs). Cases of fatal pulmonary toxicity have been reported. Delayed onset pulmonary fibrosis

Hematologic toxicity

Delayed myelosuppression. Thrombocytopenia usually occurs about 4 weeks post administration. Leukopenia occurs approximately 5–6 weeks after administration. Cumulative myelosuppression, manifested by more depressed indices. 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.

Gastrointestinal toxicity

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 side effects.

Hepatotoxicity

A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase and bilirubin levels, has been reported in a small percentage of patients.

Nephrotoxicity

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.

Implants

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.

External links

• MedlinePlus DrugInfo medmaster-a682060
• BiCNU (package insert; U.S.)