|Systematic (IUPAC) name|
|Biological half-life||5 hours|
|Excretion||40% renal (unchanged)|
|CAS Registry Number|
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Dacarbazine (//) (brand names DTIC, DTIC-Dome; also known as DIC or Imidazole Carboxamide) is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.
Dacarbazine is normally administered by intravenous infusion (IV) under the immediate supervision of a doctor or nurse. Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane, which is an alkylating agent.
As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of metastatic melanoma, and as part of the ABVD chemotherapy regimen to treat Hodgkin lymphoma, and in the MAID regimen for sarcoma. Dacarbazine was proven to be just as efficacious as procarbazine in the German trial for paediatric Hodgkin's Lymphoma, without the teratogenic effects. Thus COPDAC has replaced the former COPP regime in children for TG2 & 3 following OEPA.
Like many chemotherapy drugs, dacarbazine may have numerous serious side effects, because it interferes with normal cell growth as well as cancer cell growth. Among the most serious possible side effects are birth defects to children conceived or carried during treatment; sterility, possibly permanent; or immune suppression (reduced ability to fight infection or disease). Dacarbazine is considered to be highly emetogenic, and most patients will be pre-medicated with antiemetic drugs like palonosetron or aprepitant. Other significant side effects include headache, fatigue and occasionally diarrhea.
The Swedish National Board of Health and Welfare has sent out a Black Box Warning and suggests avoiding Dacarbazine due to liver problems.
Dacarbazine was developed by Y. Fulmer Shealy, Phd at Southern Research Institute in Birmingham, Alabama. Research was funded by a U.S. federal grant. Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by Bayer.
Bayer continues to supply DTIC-Dome. There are also generic versions of dacarbazine available from APP, Bedford, Mayne Pharma and Teva.
Diazotization of the commercially available aminoamide (5-amino-4-imidazolecarboxamide, 1) with nitrous acid gives diazonium salt (2). Rxn of this salt with dimethylamine under anhydrous conditions leads to dicarbazine (3).
- Shealy, Y. F.; Krauth, C. A.; Montgomery, J. A. (1962). "Imidazoles. I. Coupling Reactions of 5-Diazoimidazole-4-carboxamide1,2". The Journal of Organic Chemistry 27 (6): 2150. doi:10.1021/jo01053a060.
- Hano et al., Gann 59, 207 (1968), C.A. 69, 42527g (1968).