en-academic.com

Dacarbazine


Systematic (IUPAC) name
5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide
Clinical data
Trade names	Dtic-dome
AHFS/Drugs.com	monograph
MedlinePlus	a682750
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	IV
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half-life	5 hours
Excretion	40% renal (unchanged)
Identifiers
CAS number	4342-03-4
ATC code	L01AX04
PubChem	CID 2942
DrugBank	APRD00331
ChemSpider	10481959
UNII	7GR28W0FJI
KEGG	C06936
ChEMBL	CHEMBL476
Chemical data
Formula	C₆H₁₀N₆O
Mol. mass	182.18
SMILES	eMolecules & PubChem
InChI InChI=1S/C6H10N6O/c1-12(2)11-10-6-4(5(7)13)8-3-9-6/h3H,1-2H3,(H2,7,13)(H,8,9)/b11-10+ Key:FDKXTQMXEQVLRF-ZHACJKMWSA-N
(what is this?) (verify)

Dacarbazine (da-KAR-ba-zeen) (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 a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl group (C_nH_2n+1) to its DNA.

Dacarbazine is normally administered by injection (a shot) or 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".

History

Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by Bayer.

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 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.^[1]

Common 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.

Experimental

Dacarbazine + Oblimersen. In clinical trials for malignant melanoma.

Suppliers

Bayer continues to supply DTIC-Dome. There are also generic versions of dacarbazine available from APP, Bedford, Mayne Pharma and Sicor (Teva).

Sources

^ http://www.fass.se/LIF/produktfakta/audit_page.jsp?_sourcePage=%2Fproduktfakta%2Fartikel_produkt.jsp&docType=7&nplId=19971212000080

MedLine, U.S. National Institutes of Health, National Library of Medicine, http://www.nlm.nih.gov/medline/
Cancerweb, http://cancerweb.ncl.ac.uk/cancerweb/
OncoLink, http://oncolink.upenn.edu/
Swedish National Board of Health and Welfare, http://www.fass.se/LIF/produktfakta/audit_page.jsp?_sourcePage=%2Fproduktfakta%2Fartikel_produkt.jsp&docType=7&nplId=19971212000080

v · d · eIntracellular chemotherapeutic agents/antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel, Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) • Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	dihydrofolate reductase inhibitor (Aminopterin, Methotrexate, Pemetrexed, Pralatrexate) • thymidylate synthase inhibitor (Raltitrexed, Pemetrexed)

Purine	adenosine deaminase inhibitor (Pentostatin) halogenated/ribonucleotide reductase inhibitors (Cladribine, Clofarabine, Fludarabine) thiopurine (Thioguanine, Mercaptopurine)

Pyrimidine	thymidylate synthase inhibitor (Fluorouracil, Capecitabine, Tegafur, Carmofur, Floxuridine) DNA polymerase inhibitor (Cytarabine) ribonucleotide reductase inhibitor (Gemcitabine) hypomethylating agent (Azacitidine, Decitabine)

Deoxyribonucleotide	ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan)

II	Podophyllum (Etoposide, Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) • Anthracenediones (Mitoxantrone, Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine • Cyclophosphamide (Ifosfamide, Trofosfamide) • Chlorambucil (Melphalan, Prednimustine) • Bendamustine • Uramustine • Estramustine Nitrosoureas: Carmustine • Lomustine (Semustine) • Fotemustine • Nimustine • Ranimustine • Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan, Treosulfan) Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine

Alkylating-like	Platinum (Carboplatin, Cisplatin, Nedaplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin)

Nonclassical	Hydrazines (Procarbazine) • Triazenes (Dacarbazine, Temozolomide) • Altretamine • Mitobronitol

Intercalation	Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin)

Photosensitizers/PDT

Aminolevulinic acid/Methyl aminolevulinate • Efaproxiral • Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin)

Other

Enzyme inhibitors	FI (Tipifarnib) • CDK inhibitors (Alvocidib, Seliciclib) • PrI (Bortezomib) • PhI (Anagrelide) • IMPDI (Tiazofurine) • LI (Masoprocol) • PARP inhibitor (Olaparib) • HDAC (Vorinostat, Romidepsin)

Receptor antagonists	ERA (Atrasentan) • retinoid X receptor (Bexarotene) • sex steroid (Testolactone)

Other/ungrouped	Amsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)

M: NEO

tsoc, mrkr

tumr, epon, para

drug (L1i/1e/V03)