How is Lomustin (CCNU) administered?

Lomustine (CCNU) Administration Guidelines

Lomustine is administered orally as a single dose of 110-130 mg/m² once every 6 weeks. 1

Dosing and Administration Details

Lomustine (CCNU) is an oral chemotherapeutic agent from the nitrosourea class with specific administration characteristics:

• Route: Oral administration only
• Standard dosing:
  • 110-130 mg/m² as a single oral dose 1, 2
  • Administered once every 6 weeks 3, 2
• Special populations:
  • For combination therapy with bevacizumab: Dose may be reduced to 90 mg/m² every 6 weeks due to potential for increased hematologic toxicity 2

Clinical Applications

Lomustine is primarily used in the treatment of:

1. Brain tumors:

   • Component of PCV regimen (Procarbazine, CCNU/Lomustine, Vincristine) for IDH-mutant gliomas 1
   • Used in recurrent glioblastoma, either as monotherapy or in combination with bevacizumab 2

2. Specific regimens:

   • PCV regimen for oligodendrogliomas: Lomustine 110 mg/m² orally once on day 1, combined with procarbazine 60 mg/m² orally days 8-21 and vincristine 1.4 mg/m² IV on days 8 and 29 in an 8-week cycle 1
   • Can be used as monotherapy in recurrent high-grade gliomas 4

Toxicity Monitoring

Lomustine has significant delayed hematologic toxicities that require careful monitoring:

• Hematologic toxicity:

  • Causes delayed (4-6 weeks) leukopenia and thrombocytopenia 1
  • Cumulative myelosuppression can occur, requiring dose adjustments 1
  • Complete blood counts should be monitored before each cycle

• Other toxicities:

  • Pulmonary fibrosis (though less common with lomustine than with carmustine) 1
  • Nausea and vomiting (highly emetogenic) 5
  • Hepatic function should be monitored regularly 1

Antiemetic Prophylaxis

Given lomustine's high emetogenic potential:

• Recommended antiemetic regimen: Triple therapy with 5-HT3 receptor antagonist, dexamethasone, and (fos)aprepitant 5
• For oral agents with moderate to high emetic risk: Oral 5-HT3 antagonists (such as granisetron or ondansetron) with or without lorazepam and with or without either an H2 blocker or a proton pump inhibitor 1

Alternative Dosing Approaches

While the standard dosing is 110-130 mg/m² every 6 weeks, research has explored alternative schedules:

• Weekly dosing: A phase I trial investigated weekly lomustine at 30 mg/m²/week for 12+ weeks, which showed antitumor activity with manageable toxicity 3
• Combination regimens: When combined with other agents (e.g., idarubicin and dexamethasone in multiple myeloma), lower doses such as 25-50 mg/m² have been used 6

Important Considerations

• Lomustine causes delayed rather than immediate myelosuppression, with nadirs typically occurring 4-6 weeks after administration 1
• The long interval between doses (6 weeks) is designed to allow for bone marrow recovery
• Patients should carry documentation of their treatment regimen to facilitate follow-up and provide information to physicians in emergency settings 1
• Clinical centers should have standard operating procedures for managing adverse events related to lomustine therapy 1

Remember that adequate hydration and antiemetic prophylaxis are essential components of lomustine administration to improve tolerability and patient quality of life.