From the Guidelines
CCNU (Lomustine) is primarily used as a second-line treatment option for recurrent glioblastoma multiforme (GBM) after failure of first-line therapy, with a recommended dose of 100-130 mg/m² every 6 weeks as a single dose, as supported by the most recent guideline from 2022 1.
Treatment Overview
The treatment of GBM involves a multimodal approach, including surgery, radiation, and chemotherapy. Lomustine is an alkylating agent that crosses the blood-brain barrier effectively and is used as monotherapy or in combination with other agents like procarbazine and vincristine in the PCV regimen.
Dosage and Administration
The standard dose of lomustine is 100-130 mg/m² every 6 weeks as a single dose, with regular monitoring of blood counts to manage potential myelosuppression, particularly delayed thrombocytopenia and leukopenia occurring 4-6 weeks after administration.
Efficacy and Safety
While lomustine may provide modest survival benefits and temporary disease control in recurrent GBM patients, with median progression-free survival typically ranging from 2-3 months when used as monotherapy, its use is limited by potential toxicities, including myelosuppression and pulmonary fibrosis, as noted in earlier studies 1.
Clinical Recommendations
The most recent guideline from 2022 1 suggests that lomustine may be a reasonable option for treatment of recurrent GBM, although no therapy has clearly demonstrated superior activity over others in the recurrent setting, and patients should be referred for participation in a clinical trial when possible.
- Key points to consider when prescribing lomustine include:
- Regular monitoring of blood counts to manage potential myelosuppression
- Potential for delayed thrombocytopenia and leukopenia
- Limited efficacy and potential for toxicities, including pulmonary fibrosis
- Consideration of clinical trial participation for patients with recurrent GBM
From the Research
Role of CCNU in GBM Treatment
- CCNU (Lomustine) is a chemotherapeutic agent used in the treatment of Glioblastoma Multiforme (GBM) [ 2 ].
- The effectiveness of CCNU in combination with other treatments, such as bevacizumab, has been evaluated in several studies [ 3, 4,5 ].
- A network meta-analysis found that CCNU was the most common comparator and was used as the reference treatment, with no high-certainty evidence that any treatments tested were better than lomustine [ 2 ].
Efficacy of CCNU in Combination with Bevacizumab
- A retrospective study found that the combination of bevacizumab and CCNU led to an extension of progression-free survival (PFS) and overall survival (OS) compared to bevacizumab monotherapy [ 3 ].
- A meta-analysis found that the combination of lomustine and bevacizumab effectively increased OS, PFS, and 6-month PFS in patients with GBM 4.
- Another study found that the combination of lomustine and bevacizumab caused a significantly higher frequency of thrombocytopenia compared to irinotecan plus bevacizumab 5.
Current Therapies and Mechanisms of Resistance
- The standard treatment for GBMs is surgical resection followed by chemoradiotherapy, but the robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs) promote resistance against all current treatment modalities 6.
- New treatment approaches, including molecular and cellular imaging, are being developed to more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, enabling more immediate adaptation of tumor-tailored, targeted therapies 6.