Lomustine 100mg capsules

BackgroundGlioblastoma is a highly aggressive primary central nervous system tumor characterized by poor outcomes. In case of relapse or progression to adjuvant chemotherapy, there is no univocal preferred regimen for relapsing glioblastoma.MethodsWe conducted a systematic review and Bayesian trial-level network meta-analyses (NMA) to identify the regimens associated with the best outcomes. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). We estimated separate treatment rankings based on the surface under the cumulative ranking curve values. Only phase II/III prospective comparative trials were included.ResultsTwenty-four studies (3733 patients and 27 different therapies) were ultimately included. Twenty-three different regimens were compared for OS, 21 for PFS, and 26 for ORR. When taking lomustine as a common comparator, only regorafenib was likely to be significantly superior in terms of OS (hazard ratio: 0.50, 95% credible interval: 0.33-0.75). Regorafenib was significantly superior to other 16 (69.6%) regimens, including NovoTTF-100A, bevacizumab monotherapy, and several bevacizumab-based combinations. Regarding PFS and ORR, no treatment was clearly superior to the others.ConclusionsThis NMA supports regorafenib as one of the best available options for relapsing/refractory glioblastoma. Lomustine, NovoTTF-100A, and bevacizumab emerge as other viable alternative regimens. However, evidence on regorafenib is controversial at best. Moreover, most studies were underpowered, with varying inclusion criteria and primary endpoints, and no longer adapted to the most recent glioblastoma classification. A paradigmatic change in clinical trials' design for relapsing/refractory glioblastoma and more effective treatments are urgently required.

Abstract licence: CC BY-NC

IntroductionAnaplastic oligodendrogliomas are rare diffuse gliomas. Although radiotherapy (RT) combined with procarbazine, lomustine, and vincristine (PCV) has been the historical standard, temozolomide (TMZ) has been increasingly used.ObjectiveTo compare the efficacy of RT combined with PCV versus RT combined with TMZ in adult with anaplastic oligodendroglioma.MethodsA systematic search of PubMed, Embase, and the Cochrane Library was conducted up to March 2025. Eligible studies included patients with 1p/19q-codeleted anaplastic oligodendroglioma treated with RT + PCV, RT + TMZ, or RT alone. Studies comparing RT alone to RT + PCV or RT + TMZ were used to create indirect comparisons, with RT as a common comparator. A frequentist network meta-analysis with a random-effects model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS). Risk of bias was assessed with RoB 2 and ROBINS-I. The protocol was registered in PROSPERO (CRD420251012169). No funding was received.ResultsEight studies comprising 2,416 patients were included. The network meta-analysis, compared with RT alone, RT + PCV significantly improved OS (HR: 0.617; 95% CI 0.465-0.819; p = 0.0009), and PFS (HR: 0.547; 95% CI 0.415-0.721; p ConclusionIn patients with anaplastic oligodendroglioma, RT combined with PCV provides superior survival outcomes compared to radiotherapy combined with TMZ.

Abstract licence: CC BY-NC-ND

BackgroundTemozolomide (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.MethodsThree 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.ResultsIn 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.ConclusionWith 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 pointsProcarbazine-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 studyThis 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.

Abstract licence: CC BY