As of mid-2006, dacarbazine is commonly used as a single agent in the treatment of metastaticmelanoma,[5][6] and as part of the ABVDchemotherapy regimen to treat Hodgkin's lymphoma,[7] and in the MAID regimen for sarcoma.[8][9] Dacarbazine was proven to be just as efficacious as procarbazine,[10] another drug with similar chemistry, in the German trial for paediatric Hodgkin's lymphoma, without the teratogenic effects.[citation needed] Thus COPDAC has replaced the former COPP regime in children for TG2 & 3 following OEPA.[11]
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,[12] and most patients will be pre-medicated with dexamethasone and antiemetic drugs like 5-HT3 antagonist (e.g., ondansetron) and/or NK1 receptor antagonist (e.g., 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.[13]
Dacarbazine is activated by liver microsomal enzymes to monomethyl triazeno imidazole carboxamide (MTIC), which is an alkylating compound.[14] It causes methylation, modification and cross linking of DNA, thus inhibiting DNA, RNA and protein synthesis.[15]
In 1959, dacarbazine was first synthesized at Southern ResearchinAlabama.[17] 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 Bayer.
^ abcdefgh"Dacarbazine". The American Society of Health-System Pharmacists. Archived from the original on September 11, 2017. Retrieved December 8, 2016.
^World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Serrone L, Zeuli M, Sega FM, Cognetti F (March 2000). "Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview". Journal of Experimental & Clinical Cancer Research. 19 (1): 21–34. PMID10840932.
^Elias A, Ryan L, Aisner J, Antman KH (April 1990). "Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma". Seminars in Oncology. 17 (2 Suppl 4): 41–49. PMID2110385.
^Pearl ML, Inagami M, McCauley DL, Valea FA, Chalas E, Fischer M (2001). "Mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) chemotherapy for gynecological sarcomas". International Journal of Gynecological Cancer. 12 (6): 745–748. doi:10.1046/j.1525-1438.2002.01139.x. PMID12445253. S2CID25246937.
^Jelić S, Babovic N, Kovcin V, Milicevic N, Milanovic N, Popov I, et al. (February 2002). "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". Melanoma Research. 12 (1): 91–98. doi:10.1097/00008390-200202000-00013. PMID11828263. S2CID32031568.
^Kewitz S, Stiefel M, Kramm CM, Staege MS (January 2014). "Impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine resistance of Hodgkin's lymphoma cells". Leukemia Research. 38 (1): 138–143. doi:10.1016/j.leukres.2013.11.001. PMID24284332.
^"Dacarbazine". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. PMID31644220.
^Marchesi F, Turrizani M, Tortorelli G, Avvisati G, Torino F, De Vecchis L (October 2007). "Triazene compounds: Mechanism of action and related DNA repair systems". Pharmacological Research. 56 (4): 275–287. doi:10.1016/j.phrs.2007.08.003. PMID17897837.
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