Clinical outcomes of adding vincristine to procarbazine-lomustine in patients with gliomas: insights from current evidence.

Abstract

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.

Key points: Procarbazine-lomustine combination (PC) shows superior progression-free survival and overall survival versus procarbazine, lomustine and vincristine (PCV) in gliomas.Omitting vincristine may improve efficacy and reduce neurotoxicity.Findings suggest PC could be a safer alternative, pending confirmation by randomised controlled trials.

Importance of the study: This meta-analysis is the first to directly evaluate whether vincristine is necessary within the procarbazine, lomustine and vincristine (PCV) regimen for gliomas. By synthesising data from three retrospective cohorts, it demonstrates that the procarbazine-lomustine combination (PC) achieved significantly longer progression-free and overall survival compared with PCV, while markedly reducing neurotoxicity and treatment discontinuation. These findings challenge the traditional view that vincristine is an indispensable component of chemotherapy for diffuse gliomas. Given that temozolomide has become the preferred agent in contemporary practice, clarifying the relative contributions of PC, PCV and TMZ remains essential for optimising therapeutic strategies. Although limited by the small number and retrospective design of included studies, this analysis suggests that PC may represent a more effective and tolerable alternative, underscoring the need for prospective randomised trials in the modern molecular era of glioma classification.