Dacarbazine (DTIC-Dome) is activated by photode-composition and by enzymatic N-demethylation. Eventual formation of a methyl carbonium ion results in methylation of DNA and RNA and inhibition of nu-cleic acid and protein synthesis. As with other alkylating agents, cells in all phases of the cell cycle are susceptible to dacarbazine.
The plasma half-life of dacarbazine is biphasic, with a distribution phase of 19 minutes and an elimination phase of 5 hours. The drug is not appreciably protein bound, and it does not enter the central nervous system (CNS). Urinary excretion of unchanged drug is by renal tubular secretion. Dacarbazine metabolism and decom-position is complex.
Dacarbazine is the most active agent used in metasta-tic melanoma, producing a 20% remission rate. It is also combined with doxorubicin and other agents in the treat-ment of various sarcomas and Hodgkin’s disease.
Dacarbazine may cause severe nausea and vomiting. Leukopenia and thrombocytopenia occur 2 weeks after treatment, with recovery by 3 to 4 weeks. Less common is a flulike syndrome of fever, myalgias, and malaise. Alopecia and transient abnormalities in renal and he-patic function also have been reported.