Triazines (Three Attached Nitrogen Atoms).
Both temozolomide and dacarbazine form monomethyl triazine (MTIC) prior to becoming the active methylated nucleophile, methyl diazonium ion. In this setting, both O6 and N7 of guanine act as electron donors with subsequent methylation (i.e., alkylation of DNA). Dacarbazine is used (prior to targeted therapies and immunotherapies) as a single agent in the treatment of metastatic melanoma. Dacarbazine is still used as part of the ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) regimen to treat Hodgkin lymphoma and as part of the MAID (Mesna, Adriamycin, Ifosfamide, Dacarbazine) regimen for treating sarcoma. Dacarbazine can cause flu-like syndrome. Procarbazine, a close analog of dacarbazine, can cause hemolysis in G6PD-deficient patients, causing CNS depression. Temozolomide is approved for the treatment of adult patients with newly diagnosed glioblastoma multiforme (GBM) concomitantly with radiation therapy and then as maintenance treatment, as well as for the treatment of refractory anaplastic astrocytoma patients who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.