Despite various treatment approaches, recurrence, high toxicity, and poor survival persist in glioma management. This meta-analysis evaluates the efficacy and safety of biomarker-based Hydroxyurea–Imatinib therapy as a potential therapy.

Glioma is an aggressive glial tumor with high recurrence due to residual malignant cells. Hydroxyurea (HU) inhibits DNA synthesis, while Imatinib (Im) blocks aberrant signaling pathways. Together, the combination therapy (HU–Im) suppresses tumor proliferation and angiogenesis, reducing regrowth and recurrence.

Following PRISMA guidelines, we searched PubMed, Google Scholar, Cochrane, and Scopus for studies on HU–Im therapy in recurrent/progressive gliomas. Data were analyzed using OpenMeta[Analyst] software, under a random-effects model with 95% confidence intervals. Heterogeneity (I² statistic), and sensitivity analyses for I² ≥ 50% were performed. A p < 0.05 was considered significant, and risk of bias was evaluated using the Newcastle–Ottawa Scale (NOS).

We pooled data from 469 patients (281M/188F) across six studies, including five observational and one RCT. HU–Im therapy significantly improved 6-month progression-free survival to 16.6% (95% CI: 0.09–0.25; I² = 81.9%; p < 0.05). Median progression-free survival and overall survival also improved to 9.39 weeks (95% CI: 6.08–12.70; I² = 99.4%; p < 0.01) and 24.85 weeks (95% CI: 19.80–29.91; I² = 97.8%; p < 0.05), respectively. Adverse events were not significantly reduced with neutropenia (10.1%; 95% CI: 0.06–0.14; I² = 33.0%), thrombocytopenia (7.2%; 95% CI: 0.05–0.10; I² = 0%), and edema (3%; 95% CI: 0.001–0.06; I² = 28.2%) being the most common. Heterogeneity, likely from patient population, dosing, EIACD use, and evaluation was addressed via sensitivity analysis confirming consistent results.

Combination therapy demonstrated clear benefits in progressive/recurrent gliomas, improving both progression-free and overall survival. Although adverse event risk was not significantly reduced, the therapy was generally well tolerated. Larger randomized controlled trials are needed to confirm these findings.