From the Guidelines
CCNU (Lomustine) may be considered as a treatment option for glioblastoma multiforme (GBM) patients, particularly in cases where other treatments have failed, due to its ability to cross the blood-brain barrier and alkylate DNA, disrupting cancer cell replication. The use of CCNU in GBM patients is supported by evidence from studies such as 1, which suggests that nitrosourea-based chemotherapy, including CCNU, may marginally improve survival in selected patients. Key points to consider when using CCNU in GBM patients include:
- Administration: CCNU is typically administered orally at doses of 100-130 mg/m² every 6 weeks as a single dose, with dosage adjustments based on blood counts and patient tolerance.
- Monitoring: Patients require regular monitoring of blood counts, particularly 4-6 weeks after administration, as CCNU can cause delayed myelosuppression, and liver and kidney function should also be monitored.
- Mechanism of action: CCNU works by alkylating DNA, disrupting cancer cell replication and triggering cell death.
- Combination therapy: CCNU is commonly used in the PCV regimen (procarbazine, CCNU, and vincristine) for recurrent GBM or as monotherapy when temozolomide has failed. While CCNU is not curative, it can help control disease progression and potentially extend survival in patients with this aggressive brain tumor, particularly when other treatment options have been exhausted, as noted in 1.
From the Research
Role of CCNU in GBM Treatment
- CCNU (Lomustine) is a chemotherapeutic agent used in the treatment of Glioblastoma Multiforme (GBM) patients.
- A study from 1992 2 compared the effectiveness of two chemotherapy regimens, mPCV (CCNU, procarbazine, and vincristine) and VM-26 + CCNU, in patients with anaplastic astrocytoma (AA) or GBM. The results showed that mPCV produced a two-fold increase in time to tumor progression and survival time for AA patients, but not for GBM patients.
- A 2016 study 3 examined the outcome of recurrent GBM patients treated with bevacizumab (BEV) monotherapy versus BEV/CCNU therapy as last-line therapy. The results showed that BEV/CCNU treatment led to an extension of progression-free survival (PFS) and overall survival (OS) compared to BEV monotherapy.
- Another study from 2015 4 investigated the safety and feasibility of combining bevacizumab with radiotherapy and temozolomide in patients with newly diagnosed GBM. Although the study did not directly involve CCNU, it highlighted the potential of combining chemotherapeutic agents with other treatments in GBM patients.
- A 2021 network meta-analysis 5 evaluated the effectiveness of various treatments for progressive or recurrent GBM. The results suggested that lomustine (CCNU) was a common comparator and that bevacizumab plus lomustine may improve PFS, but not OS, compared to lomustine monotherapy.
- A 2009 study 6 reported on the use of ACNU-based chemotherapy for recurrent glioma in the temozolomide era. Although the study did not directly involve CCNU, it highlighted the limitations of nitrosourea-based regimens, including CCNU, in treating recurrent GBM.
Efficacy and Safety of CCNU in GBM Treatment
- The efficacy of CCNU in GBM treatment is still being researched, with some studies suggesting a potential benefit in combination with other agents, such as bevacizumab.
- The safety profile of CCNU is a concern, with studies reporting hematological toxicity and non-hematological toxicity, leading to treatment interruption in some cases.
- Further research is needed to fully understand the role of CCNU in GBM treatment and to determine the optimal combination regimens and treatment strategies.