Comparative Efficacy and Safety of Temozolomide-based Versus Lomustine-based Chemotherapy Regimens in Patients With Glioblastoma Multiforme
Govind Mann1, Sai Venkata Manoj Kotharu2, Simranjeet Nagoke3, Binay Panjiyar4, Aditi Agarwal5
1Sant Parmanand Hospital, 2Osmania Medical College, 3Government Medical College Jammu, 4Neurovascular, Northwell Health, 5Bharati Vidyapeeth University Medical College
Objective:

To compare the efficacy and safety of temozolomide– and lomustine–based chemotherapy regimens in glioblastoma multiforme through a systematic review and meta-analysis.

Background:

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor survival despite multimodal therapy. Temozolomide (TMZ) remains standard under the Stupp protocol but offers limited benefit in patients lacking O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Lomustine (CCNU), an alkylating nitrosourea, has shown potential survival gains in MGMT-methylated GBM, yet its comparative efficacy and safety remain unclear.

Design/Methods:

A systematic search of PubMed, Google Scholar, ScienceDirect, and the Cochrane Library identified cohort studies and RCTs (up to October 6, 2025). Eligible studies included adult patients (≥18 years) with histologically confirmed GBM treated with TMZ- or CCNU-based regimens. Data on overall survival (OS), progression-free survival (PFS), and treatment-related hematological and neurological toxicities were extracted. Meta-analysis using Review Manager 5.4 estimated hazard ratios for OS and PFS and risk ratios for toxicities, with 95% confidence intervals.

Results:

Among 1,115 screened articles, six met inclusion criteria for the systematic review, and four (n = 793) were eligible for meta-analysis. Pooled analysis showed no significant difference in OS between CCNU- and TMZ-based regimens (HR = 0.88; 95% CI 0.60–1.29; p = 0.52). Sensitivity analysis excluding older trials revealed a survival advantage with CCNU-based therapy (HR = 0.64; 95% CI 0.55–0.74; p < 0.00001). No significant differences were found in PFS (HR = 1.15; 95% CI 0.84–1.59; p = 0.38), hematological toxicity (RR = 1.52; p = 0.10), or neurological toxicity (RR = 1.38; p = 0.13).

Conclusions:

CCNU-based regimens may modestly improve survival over TMZ, particularly in MGMT-methylated, newly diagnosed GBM, without added toxicity. These findings support genotype-guided chemotherapy selection and highlight the need for biomarker-stratified trials to refine precision-based GBM treatment.

10.1212/WNL.0000000000217861
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