Carmustine

• Class: Alkylating agent (Nitrosourea derivative).
• Mechanism of Action:
  • Forms interstrand DNA cross-links → inhibits DNA replication and RNA/protein synthesis.
  • Lipid-soluble → readily crosses the blood-brain barrier (BBB).
• Clinical Uses:
  • Primary brain tumors (gliomas, astrocytoma, medulloblastoma, glioblastoma multiforme).
  • Secondary CNS involvement by lymphoma or multiple myeloma.
  • Hodgkin’s and non-Hodgkin’s lymphoma (part of regimens like BEAM for stem cell transplant conditioning).
• Dosing:
  • IV: typically 150–200 mg/m² as a single dose every 6 weeks, or divided doses over 2 days (max cumulative dose must be monitored due to toxicity).
  • Also available as carmustine wafer (Gliadel®) for direct implantation in brain tumors.
• Toxicities:
  • Dose-limiting: Delayed myelosuppression (nadir at 4–6 weeks, recovery 6–8 weeks).
  • Pulmonary toxicity (interstitial fibrosis) – risk increases with cumulative doses (>1400 mg/m²), younger patients, and long-term use.
  • Hepatotoxicity and nephrotoxicity.
  • Nausea/vomiting (highly emetogenic).
• Monitoring:
  • CBC (weekly for at least 6 weeks after dosing).
  • Pulmonary function tests (baseline and periodically).
  • Renal and liver function.
  • Cumulative dose to minimize risk of pulmonary fibrosis.

In summary: Carmustine is a nitrosourea alkylating agent with strong CNS penetration, widely used in brain tumors and transplant regimens. Key concerns are delayed myelosuppression and dose-dependent pulmonary fibrosis.