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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/12 23:11:58」(JST)

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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.

Uses[edit]

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 chemotherapeutic protocol to prepare for hematological stem cell transplantation, to reduce the white blood cells in the recipient (patient). This use under this protocol, usually with Fludarabine and Melphalan, was coined by oncologist at MD Anderson Cancer Center.

Side effects[edit]

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.

Implants[edit]

In the treatment of brain tumours, the U.S. Food and Drug Administration (FDA) approved biodegradable discs, Gliadel, infused with carmustine can be used.^[2] They are implanted under the skull during a surgery called a craniotomy.^[3]

References[edit]

^ "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.
^ http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualdrugs/Gliadelimplants

External links[edit]

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

UpToDate Contents

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English Journal

Treatment of glioblastoma multiforme with high doses of carmustine intracavitary, in an infant.

Rivero-Garvía M, Márquez-Rivas J, Rueda-Torres AB, Pascual-Argente D, Ramírez G.SourcePediatric Neurosurgery Unit, Department of Neurosurgery, Virgen del Rocío Hospital, Manuel Siruot s/n 41013, Seville, Spain, monicagarvia@msn.com.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery.Childs Nerv Syst.2012 May;28(5):747-50. Epub 2011 Dec 29.
PMID 22205534

NICE guidance on the use of carmustine wafers in high grade gliomas: a national study on variation in practice.

Price SJ, Whittle IR, Ashkan K, Grundy P, Cruickshank G.SourceDepartment of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital , Cambridge , UK.
British journal of neurosurgery.Br J Neurosurg.2012 Apr 6. [Epub ahead of print]
Background. Multidisciplinary team (MDT) working in oncology aims to improve outcomes for patients with cancer. One role is to ensure the implementation of best practice and National Institute for Health and Clinical Excellence (NICE) guidance. In this study, we have assessed the role of MDT in impl
PMID 22482926

Japanese Journal

A Multicenter Phase I/II Study of the BCNU Implant (Gliadel® Wafer) for Japanese Patients with Malignant Gliomas

AOKI Tomokazu,NISHIKAWA Ryo,SUGIYAMA Kazuhiko,NONOGUCHI Naosuke,KAWABATA Noriyuki,MISHIMA Kazuhiko,ADACHI Jun-ichi,KURISU Kaoru,YAMASAKI Fumiyuki,TOMINAGA Teiji,KUMABE Toshihiro,UEKI Keisuke,HIGUCHI Fumi,YAMAMOTO Tetsuya,ISHIKAWA Eiichi,TAKESHIMA Hideo,YAMASHITA Shinji,ARITA Kazunori,HIRANO Hirofumi,YAMADA Shinobu,MATSUTANI Masao,for the NPC-08 study group
Neurologia medico-chirurgica 54(4), 290-301, 2014
… Carmustine (BCNU) implants (Gliadel® Wafer, Eisai Inc., New Jersey, USA) for the treatment of malignant gliomas (MGs) were shown to enhance overall survival in comparison to placebo in controlled clinical trials in the United States and Europe. …
NAID 130003383270

海外の新薬審査情報を読み解く(第13回)カルムスチン(Carmustine)

野村香織
月刊薬事 = The pharmaceuticals monthly 55(1), 147-150, 2013-01
NAID 40019548318

Second-line chemotherapy with irinotecan plus carmustine in glioblastoma recurrent or progressive after first-line temozolomide chemotherapy : a phase II study of the Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO)

BRANDES AA
J. Clin. Oncol. 22, 4779-4786, 2004
NAID 30022791313

Related Pictures

★リンクテーブル★

リンク元	「カルムスチン」「BCNU」「BiCNU」

「カルムスチン」

Carmustine
	IUPAC name 1,3-Bis(2-chloroethyl)-1-nitrosourea
	Other names N,N’-Bis(2-chloroethyl)-N-nitroso-urea[citation needed]
Identifiers
CAS number	154-93-8
PubChem	2578
ChemSpider	2480
UNII	U68WG3173Y
EC number	205-838-2
UN number	2811
DrugBank	DB00262
KEGG	D00254
MeSH	Carmustine
ChEBI	CHEBI:3423
ChEMBL	CHEMBL513
RTECS number	YS2625000
ATC code	L01AD01
Jmol-3D images
	SMILES 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) ; Key: DLGOEMSEDOSKAD-UHFFFAOYSA-N ;
Properties
Molecular formula	C5H9Cl2N3O2
Molar mass	214.05 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; Allantoic acid; Buformin;
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references