Dacarbazine (DTIC), also known as imidazole carboxamide, is a chemotherapy medication used in the treatment of melanoma and Hodgkin's lymphoma. For Hodgkin's it is often used together with vinblastine,

bleomycin -13- (1''H''-imidazol-5-yl)methyl9-hydroxy-5- 1''R'')-1-hydroxyethyl8,10-dimethyl-4,7,12,15-tetraoxo-3,6,11,14-tetraazapentadec-1-yl}-2,4'-bi-1,3-thiazol-4-yl)carbonyl]amino}propyl)(dimethyl)sulfonium , chemical_formula = , C=55 , H=84 , N=1 ...

, and doxorubicin. It is given by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

. Common side effects include loss of appetite, vomiting, low white blood cell count, and low platelets. Other serious side effects include liver problems and allergic reactions. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

is safe for the baby. Dacarbazine is in the

alkylating agent Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effectin ...

and

purine analog Purine analogues are antimetabolites that mimic the structure of metabolic purines. Examples * Nucleobase analogues **Thiopurines such as thioguanine are used to treat acute leukemias and remissions in acute granulocytic leukemias. ***Azathioprine ...

families of medication. Dacarbazine was approved for medical use in the United States in 1975. It is on the World Health Organization's List of Essential Medicines.

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 A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combina ...

to treat Hodgkin's lymphoma, and in the MAID regimen for sarcoma. Dacarbazine was proven to be just as efficacious as procarbazine, another drug with similar chemistry, 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 (reduced ability to fight infection or disease). Dacarbazine is considered to be highly emetogenic, and most patients will be pre-medicated with

dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...

and antiemetic drugs like 5-HT₃ antagonist (e.g., ondansetron) and/or NK₁ receptor antagonist (e.g.,

aprepitant Aprepitant, sold under the brand name Emend among others, is a medication used to prevent chemotherapy-induced nausea and vomiting (CINV) and to prevent postoperative nausea and vomiting (PONV). It may be used together with ondansetron and de ...

). 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 In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that i ...

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 methylated 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. Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane, which is an

Synthesis

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.

Suppliers

Bayer continues to supply DTIC-Dome. There are also

generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

versions of dacarbazine available from APP, Bedford, Mayne Pharma (now Hospira) and Teva.

References

External links

* {{portal bar, Medicine Hepatotoxins Imidazoles DNA replication inhibitors IARC Group 2B carcinogens Carboxamides Teratogens World Health Organization essential medicines Cancer treatments Wikipedia medicine articles ready to translate