Dacarbazine

 Class: Alkylating-like agent (Triazene derivative).

• Mechanism of Action:
  • Prodrug → requires hepatic activation by CYP450 to MTIC (monomethyl triazeno imidazole carboxamide).
  • MTIC causes DNA methylation at the O6 and N7 positions of guanine → leads to mispairing and strand breakage → inhibition of DNA replication and function.
• Clinical Uses:
  • Hodgkin’s lymphoma (part of ABVD regimen: Adriamycin, Bleomycin, Vinblastine, Dacarbazine).
  • Metastatic malignant melanoma (historically standard before immune checkpoint inhibitors and targeted therapies).
  • Soft tissue sarcomas.
  • Neuroblastoma and other investigational uses.
• Dosing:
  • IV, varies by indication:
    • 150–250 mg/m²/day for 5 days, every 3 weeks, or
    • 850 mg/m² every 3 weeks (melanoma).
  • Requires antiemetic prophylaxis (highly emetogenic in high doses).
• Toxicities:
  • Myelosuppression (dose-limiting; leukopenia, thrombocytopenia).
  • Severe nausea and vomiting (highly emetogenic).
  • Flu-like symptoms (fever, malaise, myalgias).
  • Hepatotoxicity – rare but serious veno-occlusive disease (VOD).
  • Injection site pain (given IV, often with central line to reduce extravasation risk).
• Monitoring:
  • CBC (weekly during treatment cycles).
  • Liver function tests (risk of VOD).
  • Monitor for N/V and premedicate with antiemetics.

In summary:

Dacarbazine is a triazene alkylating-like agent used mainly in Hodgkin’s lymphoma (ABVD) and melanoma. It requires hepatic activation, is highly emetogenic, and carries risks of myelosuppression and rare but serious veno-occlusive disease.