Lomustine — Drug Monograph

Brand names: Gleostine, CCNU

Drug class: Alkylating Agent

Mechanism of Action

Lomustine is a highly lipid-soluble nitrosourea alkylating agent that undergoes spontaneous non-enzymatic decomposition to form reactive metabolites. These metabolites produce DNA alkylation and cross-linking, which interferes with DNA template function and protein synthesis. As a cell-cycle non-specific agent, it affects cells in all phases but is most active in the S phase. Its ability to cross the blood-brain barrier is attributed to its high lipophilicity and lack of ionization at physiological pH.

FDA Indications

• Brain tumors (both primary and metastatic) in patients who have already received appropriate surgical and/or radiotherapeutic procedures
• Hodgkin’s disease (as secondary therapy in combination with other approved drugs)

Common Side Effects

• Nausea
• Vomiting
• Delayed myelosuppression
• Anorexia
• Alopecia
• Stomatitis

Clinical Pearl

Lomustine is unique due to its strictly oral administration and the extreme delay in hematologic nadir, which typically occurs at 4 to 6 weeks for leukocytes and platelets. Because of the risk of fatal dosing errors, it is critical that only one dose (one cycle) is dispensed at a time, and patients are clearly instructed NOT to take it daily. Nausea and vomiting are common but usually transient, occurring 3 to 6 hours after dosing; prophylactic antiemetics are highly recommended. Long-term use…

Related Therapies & Mechanisms

• Carmustine (BiCNU) — Alkylating Agent · Lymphoma
• Bendamustine (Treanda) — Alkylating Agent · Lymphoma
• Chlorambucil (Leukeran) — Alkylating Agent · Lymphoma
• Cyclophosphamide (Cytoxan) — Alkylating Agent · Lymphoma