Background Temozolomide (TMZ) is the standard chemotherapy for gliomas due to good tolerability. Clinical studies suggest a combination of procarbazine, lomustine (CCNU) and vincristine (PCV) provides superior survival and progression delay, but toxicities limit use. Given the ongoing debate over the role of vincristine in glioma chemotherapy amid the dominance of TMZ, simplified procarbazine and CCNU (PC) regimens warrant renewed evaluation.

Methods Three databases were searched up to August 2025 to identify studies that directly compared PC and PCV in patients with low-grade and high-grade gliomas. Outcomes included progression-free survival (PFS), overall survival (OS) and treatment-related toxicities. Hazard ratios (HRS) and relative risks (RRS) were then pooled using a random-effects model.

Results In a total population of 301 patients with low- and high-grade gliomas, PC significantly reduced the risk of disease progression compared with PCV (HR = 0.72, 95% confidence interval (CI): 0.53–0.98; p = 0.04) and OS was also significantly longer with PC (HR = 0.59, 95% CI: 0.37–0.95; p = 0.03). Neurotoxicity (RR = 0.12, 95% CI: 0.02–0.63; p = 0.01) and treatment discontinuation (RR = 0.11, 95% CI: 0.02–0.80; p = 0.03) were less frequent with PC.

Conclusion With the limited evidence available to date, we found that PC achieved significantly longer PFS and OS than PCV, while maintaining a better safety profile. We recommend further well-designed and adequately powered randomised clinical trials directly comparing TMZ, PC and PCV to determine which patient populations and glioma subtypes – according to the current World Health Organisation 2021 classification – derive the greatest survival benefit and tolerability from each regimen.