Lomustine

• Class: Alkylating agent – Nitrosourea derivative.
• Mechanism of Action:
  • Alkylates DNA and RNA → causes interstrand cross-links and strand breaks → inhibits replication and transcription.
  • Highly lipophilic, easily crosses the blood–brain barrier, making it useful in CNS malignancies.
• Clinical Uses:
  • Primary and metastatic brain tumors (glioblastoma, astrocytoma, medulloblastoma).
  • Part of combination regimens in Hodgkin’s lymphoma (e.g., part of salvage therapy).
• Dosing:
  • Oral, usually 100–130 mg/m² as a single dose every 6–8 weeks.
  • Dose adjustment required for renal or hepatic impairment.
• Toxicities:
  • Delayed myelosuppression (nadir 4–6 weeks, recovery 6–8 weeks) – dose-limiting.
  • Pulmonary toxicity (interstitial fibrosis, risk with cumulative dose >1100–1200 mg/m²).
  • Hepatotoxicity and nephrotoxicity (with cumulative use).
  • CNS effects (ataxia, confusion, seizures – rare, but possible due to CNS penetration).
  • Nausea/vomiting (moderately emetogenic).
• Monitoring:
  • CBC weekly × 6 weeks after each dose.
  • Baseline and periodic pulmonary function tests.
  • Renal and liver function.
  • Track cumulative dose to minimize pulmonary and hepatic fibrosis risk.

In summary: Lomustine is an oral nitrosourea alkylating agent with excellent CNS penetration, used mainly for brain tumors and Hodgkin’s lymphoma. Major concerns are delayed myelosuppression and cumulative pulmonary fibrosis.