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 Carmustine

Carmustine is  antineoplastic nitrosourea. Carmustine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. This agent also carbamoylates proteins, including DNA repair enzymes, resulting in an enhanced cytotoxic effect. Carmustine is highly lipophilic and crosses the blood-brain barrier readily. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

BiCNU® (carmustine for injection) is one of the nitrosoureas used in the treatment of certain neoplastic diseases. It is 1,3-bis (2-chloroethyl)-1-nitrosourea. It is sterile lyophilized pale yellow flakes or congealed mass with a molecular weight of 214.06. It is highly soluble in alcohol and lipids, and poorly soluble in water. BiCNU is administered by intravenous infusion after reconstitution as recommended.  BiCNU is available in 100 mg single dose vials of lyophilized material. Sterile diluent for constitution of BiCNU is co-packaged with the active drug product for use in constitution of the lyophile. The diluent is supplied in an ampule containing 3 mL of Dehydrated Alcohol Injection, USP.

Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross-resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.

Intravenously administered carmustine is rapidly degraded, with no intact drug detectable after 15 minutes. However, in studies with 14C-labeled drug, prolonged levels of the isotope were detected in the plasma and tissue, probably representing radioactive fragments of the parent compound.

It is thought that the antineoplastic and toxic activities of carmustine may be due to metabolites. Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2. The fate of the remainder is undetermined.

Because of the high lipid solubility and the relative lack of ionization at physiological pH, carmustine crosses the blood-brain barrier quite effectively. Levels of radioactivity in the CSF are ≥50% of those measured concurrently in plasma.

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52: Zekri JM, Mouncey P, Hancock BW. Trials in advanced Hodgkin's disease: more than 30 years experience of the British National Lymphoma Investigation. Clin Lymphoma. 2004 Dec;5(3):174-83. Review. PubMed PMID: 15636693.

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73: Roth TJ, Xu Y, Luo M, Kelley MR. Human-yeast chimeric repair protein protects mammalian cells against alkylating agents: enhancement of MGMT protection. Cancer Gene Ther. 2003 Aug;10(8):603-10. PubMed PMID: 12872142.

74: Martin AG. Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. J Drugs Dermatol. 2003 Apr;2(2):155-67. Review. PubMed PMID: 12852367.

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86: Li Y, McClay EF. Systemic chemotherapy for the treatment of metastatic melanoma. Semin Oncol. 2002 Oct;29(5):413-26. Review. PubMed PMID: 12407507.

87: Labar B, Bogdanić V, Nemet D, Mrsić M, Serventi-Seiwerth R, Sertić D, Golubić-Cepulić B, Vrtar M, Santek F, Batinić D, Mikulić M, Pulanić D. Allogeneic stem cell transplantation in treatment of aggressive lymphomas: case series. Croat Med J. 2002 Oct;43(5):565-8. PubMed PMID: 12402397.

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92: Sun W, Schuchter LM. Metastatic melanoma. Curr Treat Options Oncol. 2001 Jun;2(3):193-202. Review. PubMed PMID: 12057119.

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