CeeNU / Gleostine

Brain tumors — both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures; Hodgkin lymphoma — as secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.

130 mg/m² orally as a single dose every 6 weeks
Adjust based on nadir blood counts from prior dose:
• Leukocytes ≥3,000 and platelets ≥75,000: give 100% of dose
• Leukocytes 2,000-2,999 or platelets 25,000-74,999: give 70% of dose
• Leukocytes <2,000 or platelets <25,000: give 50% of dose
Take on empty stomach. Do not give more frequently than every 6 weeks due to delayed and cumulative myelosuppression.

Capsules: 5 mg, 10 mg, 40 mg, 100 mg (dose pack containing various capsule strengths)

Hypersensitivity to lomustine or any component.

• Myelosuppression: Dose-limiting. Thrombocytopenia (nadir ~4 weeks, recovery 5-6 weeks) and leukopenia (nadir ~5-6 weeks, recovery 6-7 weeks). Cumulative with repeated courses. Monitor CBC weekly for at least 6 weeks after each dose.
• Pulmonary Toxicity: Pulmonary infiltrates and/or fibrosis with cumulative doses >1,100 mg/m². Can be fatal. Onset may be delayed years after treatment.
• Hepatotoxicity: Reversible increases in transaminases, alkaline phosphatase, and bilirubin reported.
• Nephrotoxicity: Decrease in kidney size, progressive azotemia, and renal failure reported with large cumulative doses.
• Secondary Malignancies: Acute leukemia and myelodysplasia reported.

Nausea and vomiting (within 3-6 hours, lasting 24 hours), thrombocytopenia (65%), leukopenia (63%), anemia (common), stomatitis (5%), alopecia (common), hepatotoxicity (transient, reversible), pulmonary toxicity (dose-cumulative)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Lomustine (CCNU) is a nitrosourea alkylating agent that undergoes spontaneous chemical decomposition to form reactive intermediates. These intermediates alkylate DNA and RNA, forming interstrand cross-links and single-strand breaks. The chloroethyl moiety generates chloroethyl-diazonium ions that alkylate DNA at the O6-position of guanine, producing O6-chloroethylguanine adducts that rearrange to form interstrand cross-links. It also carbamoylates proteins, including DNA repair enzymes. Being highly lipophilic, lomustine readily crosses the blood-brain barrier.

Rapidly absorbed orally. Extensively metabolized hepatically (CYP enzymes) to active metabolites. Half-life of metabolites: 16-48 hours. Crosses blood-brain barrier (CSF levels 15-30% of plasma). Primarily excreted renally (50% within 12 hours).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• CeTeG/NOA-09 — Lomustine + temozolomide vs. temozolomide in MGMT-methylated glioblastoma. Phase III, n=141.
  🔬 NCT01149109 ↗ 📄 Primary Publication ↗

CeeNU / Gleostine has FDA-approved indications across the following cancer types covered on PipelineEvidence: