Dacarbazine 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 a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl group to its DNA. Dacarbazine is normally administered by intravenous infusion 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. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. Medical uses 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.
Side effects 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. 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. Mechanism of Action Dacarbazine works by methylating guanine at the O-6 and N-7 positions. Guanine is one of the four nucleotides that makes up DNA.
The alkylated DNA strands stick together such that cell division becomes impossible. This affects cancer cells more than healthy cells because cancer cells divide faster. Unfortunately however, some of the healthy cells will still be damaged. History 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. Experimental Dacarbazine + Oblimersen. In clinical trials for malignant melanoma.01 Suppliers Bayer continues to supply DTIC-Dome. There are also generic versions of dacarbazine available from APP, Bedford, Mayne Pharma and Teva. See also Melanoma Hodgkin disease ABVD History of cancer chemotherapy Alkylating antineoplastic agent Notes References.
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