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Revision as of 11:56, 2 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit		Latest revision as of 23:06, 26 January 2024 edit undoMaxim Masiutin (talk | contribs)Extended confirmed users, IP block exemptions, Pending changes reviewers31,043 edits Removed 3 display-authors attributes from cite entries that match that of "cs1 config" to exclude the article from Category:CS1 maint: overridden setting. Used lowercase "cite" template everywhere for consistency, as the majority of instances used lowercase already.
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			{{Short description|Chemotherapy medication}}
			{{Use mdy dates|date=September 2023}}
			{{cs1 config |name-list-style=vanc |display-authors=6}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Verifiedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 401977136		| verifiedrevid = 458622631
⚫	| IUPAC_name = 5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide
	| image = Dacarbazine structure.png		| image = Dacarbazine.svg
			| width = 175
			| alt =
	<!--Clinical data-->		<!--Clinical data-->
			| pronounce = {{IPAc-en|d|ə|ˈ|k|ɑr|b|ə|ˌ|z|iː|n}}
	| tradename = Dtic-dome		| tradename = DTIC-Dome, others
	| Drugs.com = {{drugs.com|monograph|dacarbazine}}		| Drugs.com = {{drugs.com|monograph|dacarbazine}}
	| MedlinePlus = a682750		| MedlinePlus = a682750
		⚫	| routes_of_administration = ]
	| pregnancy_category = C
		⚫	| ATC_prefix = L01
		⚫	| ATC_suffix = AX04
			| legal_US = Rx-only
	| legal_status = Rx-only		| legal_status = Rx-only
⚫	| routes_of_administration = IV
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = ?		| bioavailability = 100%
	| metabolism = ?		| metabolism = Extensive
			| metabolites =
	| elimination_half-life = 5 hours		| elimination_half-life = 5 hours
	| excretion = 40% renal (unchanged)		| excretion = ] (40% as unchanged dacarbazine)
	<!--Identifiers-->		<!--Identifiers-->
⚫	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 4342-03-4		| CAS_number = 4342-03-4
⚫	| ATC_prefix = L01
⚫	| ATC_suffix = AX04
	| PubChem = 2942		| PubChem = 2942
		⚫	| ChEBI_Ref = {{ebicite|changed|EBI}}
			| ChEBI = 4305
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00851		| DrugBank = DB00851
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	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 7GR28W0FJI		| UNII = 7GR28W0FJI
	| KEGG_Ref = {{keggcite|changed|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = C06936		| KEGG = D00288
			| KEGG2 = C06936
⚫	| ChEMBL_Ref = {{ebicite|changed|EBI}}
		⚫	| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 476		| ChEMBL = 476
			| synonyms = DTIC<ref>{{cite book| veditors = Elks J, Ganellin CR |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|date=1990|publisher=Springer|doi=10.1007/978-1-4757-2085-3|pages=344–| isbn = 978-1-4757-2087-7 }}</ref>
	<!--Chemical data-->		<!--Chemical data-->
		⚫	| IUPAC_name = 5-(3,3-Dimethyl-1-triazenyl)imidazole-4-carboxamide
	| C=6 | H=10 | N=6 | O=1		| C=6 | H=10 | N=6 | O=1
	| molecular_weight = 182.18
	| smiles = CN(C)/N=N/c1ncnc1C(N)=O		| smiles = CN(C)N=Nc1cnc1C(N)=O
	| InChI = 1/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+
	| InChIKey = FDKXTQMXEQVLRF-ZHACJKMWBK
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 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+		| StdInChI = 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+
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	| StdInChIKey = FDKXTQMXEQVLRF-ZHACJKMWSA-N		| StdInChIKey = FDKXTQMXEQVLRF-ZHACJKMWSA-N
	}}		}}
	'''Dacarbazine''' (da-KAR-ba-zeen) (brand names DTIC, DTIC-Dome; also known as DIC or Imidazole Carboxamide) is an antineoplastic ] drug used in the treatment of various cancers, among them ], ], ], and islet cell carcinoma of the pancreas.
			<!-- Definition and medical uses -->
	Dacarbazine is a member of the class of ]s, which destroy cancer cells by adding an ] group (C<sub>n</sub>H<sub>2n+1</sub>) to its ].
			'''Dacarbazine''', also known as '''imidazole carboxamide''' and sold under the brand name '''DTIC-Dome''', is a ] used in the treatment of ] and ].<ref name=AHFS2016/> For Hodgkin's lymphoma it is often used together with ], ], and ].<ref name=AHFS2016/> It is given by ].<ref name=AHFS2016>{{cite web|title=Dacarbazine|url=https://www.drugs.com/monograph/dacarbazine.html|publisher=The American Society of Health-System Pharmacists|access-date=December 8, 2016|url-status=live|archive-url=https://web.archive.org/web/20170911072711/https://www.drugs.com/monograph/dacarbazine.html|archive-date=September 11, 2017}}</ref>
			<!-- Side effects and mechanism -->
	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 ], which is an "alkylating agent".
			Common side effects include loss of appetite, vomiting, ], and ].<ref name=AHFS2016/> Other serious side effects include ] and ].<ref name=AHFS2016/> It is unclear if use in ] is safe for the baby.<ref name=AHFS2016/> Dacarbazine is in the ] and ] families of medication.<ref name=AHFS2016/>
	==History==		<!-- History and culture -->
			Dacarbazine was approved for medical use in the United States in 1975.<ref name=AHFS2016/> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
⚫	{{see also|History of cancer chemotherapy}}
	Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by ].
			==Medical uses==
			As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of ] ],<ref>{{cite journal | vauthors = Serrone L, Zeuli M, Sega FM, Cognetti F | title = Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview | journal = Journal of Experimental & Clinical Cancer Research | volume = 19 | issue = 1 | pages = 21–34 | date = March 2000 | pmid = 10840932 }}</ref><ref>{{cite journal | vauthors = Bhatia S, Tykodi SS, Thompson JA | title = Treatment of metastatic melanoma: an overview | journal = Oncology | volume = 23 | issue = 6 | pages = 488–496 | date = May 2009 | pmid = 19544689 | pmc = 2737459 }}</ref> and as part of the ] ] to treat ],<ref>{{cite journal | vauthors = Rueda Domínguez A, Márquez A, Gumá J, Llanos M, Herrero J, de Las Nieves MA, Miramón J, Alba E | title = Treatment of stage I and II Hodgkin's lymphoma with ABVD chemotherapy: results after 7 years of a prospective study | journal = Annals of Oncology | volume = 15 | issue = 12 | pages = 1798–1804 | date = December 2004 | pmid = 15550585 | doi = 10.1093/annonc/mdh465 | doi-access = free }}</ref> and in the MAID regimen for ].<ref>{{cite journal | vauthors = Elias A, Ryan L, Aisner J, Antman KH | title = Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma | journal = Seminars in Oncology | volume = 17 | issue = 2 Suppl 4 | pages = 41–49 | date = April 1990 | pmid = 2110385 }}</ref><ref>{{cite journal | vauthors = Pearl ML, Inagami M, McCauley DL, Valea FA, Chalas E, Fischer M | title = Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for gynecological sarcomas | journal = International Journal of Gynecological Cancer | volume = 12 | issue = 6 | pages = 745–748 | date = 2001 | pmid = 12445253 | doi = 10.1046/j.1525-1438.2002.01139.x | s2cid = 25246937 }}</ref> Dacarbazine was proven to be just as efficacious as ],<ref>{{cite journal | vauthors = Jelić S, Babovic N, Kovcin V, Milicevic N, Milanovic N, Popov I, Radosavljevic D | title = Comparison of the efficacy of two different dosage dacarbazine-based regimens and two regimens without dacarbazine in metastatic melanoma: a single-centre randomized four-arm study | journal = Melanoma Research | volume = 12 | issue = 1 | pages = 91–98 | date = February 2002 | pmid = 11828263 | doi = 10.1097/00008390-200202000-00013 | s2cid = 32031568 }}</ref> another drug with similar chemistry, in the German trial for paediatric Hodgkin's lymphoma, without the teratogenic effects.{{citation needed|date=August 2016}} Thus COPDAC has replaced the former COPP regime in children for TG2 & 3 following OEPA.<ref>{{cite journal | vauthors = Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D | title = Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study | journal = Journal of Clinical Oncology | volume = 28 | issue = 23 | pages = 3680–3686 | date = August 2010 | pmid = 20625128 | doi = 10.1200/jco.2009.26.9381 | doi-access = free }}</ref>
	==Side effects==		==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 ], and most patients will be pre-medicated with antiemetic drugs like ] or ]. Other significant side effects include headache, fatigue and occasionally diarrhea.		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 ],<ref>{{cite journal | vauthors = Aoki S, Iihara H, Nishigaki M, Imanishi Y, Yamauchi K, Ishihara M, Kitaichi K, Itoh Y | title = Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant | journal = Molecular and Clinical Oncology | volume = 1 | issue = 1 | pages = 41–46 | date = January 2013 | pmid = 24649120 | pmc = 3956247 | doi = 10.3892/mco.2012.15 }}</ref> and most patients will be pre-medicated with ] and antiemetic drugs like ] (e.g., ]) and/or ] (e.g., ]). 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.<ref>http://www.fass.se/LIF/produktfakta/audit_page.jsp?_sourcePage=%2Fproduktfakta%2Fartikel_produkt.jsp&docType=7&nplId=19971212000080</ref>		The Swedish National Board of Health and Welfare has sent out a ] and suggests avoiding dacarbazine due to liver problems.<ref>{{cite web|url=http://www.fass.se/LIF/produktfakta/audit_page.jsp?_sourcePage%3D%2Fproduktfakta%2Fartikel_produkt.jsp%26docType%3D7%26nplId%3D19971212000080 | title = Alla aktuella ändringar för Dacarbazine medac Pulver till infusionsvätska, lösning 500 mg, Medac | work = FASS.se |access-date=August 19, 2011 |url-status=dead |archive-url=https://web.archive.org/web/20111001011425/http://www.fass.se/LIF/produktfakta/audit_page.jsp?_sourcePage=%2Fproduktfakta%2Fartikel_produkt.jsp&docType=7&nplId=19971212000080 |archive-date=October 1, 2011 }}</ref>
	==Common uses==		==Mechanism of action==
			Dacarbazine is activated by liver microsomal enzymes to monomethyl triazeno imidazole carboxamide (MTIC), which is an ].<ref>{{cite journal | vauthors = Kewitz S, Stiefel M, Kramm CM, Staege MS | title = Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine resistance of Hodgkin's lymphoma cells | journal = Leukemia Research | volume = 38 | issue = 1 | pages = 138–143 | date = January 2014 | pmid = 24284332 | doi = 10.1016/j.leukres.2013.11.001 }}</ref> It causes methylation, modification and cross linking of DNA, thus inhibiting DNA, RNA and protein synthesis.<ref>{{cite book |title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |year=2012 |chapter=Dacarbazine |pmid=31644220}}</ref>
	As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of ] ], and as part of the ] ] to treat ], and in the MAID regimen for sarcoma.
	==Experimental==		==Synthesis==
			] is added to 5-aminoimidazol-4-carboxamide to make 5-diazoimidazol-4-carboxamide. It reacts with ] to give dacarbazine.<ref>{{cite book |title=Synthesis of Essential Drugs |vauthors=Vardanyan RS, Hruby VJ |year=2006 |pages=389–418 |chapter=30 - Antineoplastics |doi=10.1016/B978-044452166-8/50030-3|isbn=9780444521668 }}</ref>
	Dacarbazine + ]. In clinical trials for malignant ].
			]
	==Suppliers==		==History==
		⚫	{{see also|History of cancer chemotherapy}}
⚫	Bayer continues to supply DTIC-Dome. There are also generic versions of dacarbazine available from APP, Bedford, Mayne Pharma and Sicor (]).
			In 1959, dacarbazine was first synthesized at ] in ].<ref>{{cite journal |vauthors=Marchesi F, Turrizani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L |date=October 2007 |title=Triazene compounds: Mechanism of action and related DNA repair systems |journal=Pharmacological Research |volume=56 |issue=4 |pages=275–287 |doi=10.1016/j.phrs.2007.08.003|pmid=17897837 }}</ref> The research was funded by a US federal grant. Dacarbazine gained FDA approval in May 1975 as DTIC-Dome. The drug was initially marketed by ].
			==Society and culture ==
	==See also==
			{{unreferenced section|date=September 2023}}
	* ]
		⚫	There are ] versions of dacarbazine available from APP, Bedford, Mayne Pharma (]) and ].
	* ]
	* ]
	* ]
	* ]
	==Sources==		== References ==
	{{Reflist}}		{{Reflist}}
	*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
	{{Chemotherapeutic agents}}		{{Chemotherapeutic agents}}
			{{Portal bar|Medicine}}
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