Granulocyte-macrophage colony stimulating factor enhances efficacy of nimustine rendezvousing with temozolomide plus irradiation in patients with glioblastoma.

BACKGROUND: Glioblastoma is the most common and most aggressive type of primary brain tumor. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of intranasal granulocyte-macrophage colony stimulating factor (GM-CSF) administration combined with chemoradiotherapy in patients with glioblastoma who underwent surgery. METHODS: Ninety-two patients were randomly divided into two groups: a control group (n= 46), who received radiotherapy with adjuvant local delivery of nimustine hydrochloride (ACNU) and systemic administration of temozolomide, and an intervention group (n= 46), who received intranasal GM-CSF prior to each cycle of adjuvant chemotherapy in addition to the treatment of the control group. Karnofsky performance status (KPS) scores, progression-free survival (PFS), overall survival (OS), and adverse effects were calculated and compared between the two groups. RESULTS: Compared with the control group, the intervention group had longer PFS (7.8 vs. 6.9 months, P= 0.016) and OS (19.2 vs. 17.1 months, P= 0.045, without adjustment for interim analyses). The KPS scores were also higher in the intervention group than in the control group after 6 months (84.35 ± 8.86 vs. 80.65 ± 7.72; t= 4.552, P= 0.036). Furthermore, the patients in the intervention group had lower incidence of neutropenia and thrombocytopenia (8.7% vs. 29.5%, P= 0.012; 8.7% vs. 18.2%, P= 0.186). Other adverse events were similar in both groups, and most adverse events were grade I/II and resolved spontaneously. CONCLUSION: Intranasal GM-CSF enhances the efficacy of the local ACNU administration combined with oral temozolomide chemotherapy. The survival and performance status were significantly improved in patients with glioblastoma after surgery. Additionally, the GM-CSF therapy was able to reduce the occurrence of chemotherapy-related neutropenia and thrombocytopenia.

[Network pharmacology study on potential active components in volatile oil of Dictamni Cortex].

There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of "component-target-disease" can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build "component-target-disease" network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.

Enhanced antitumor effects of radiotherapy combined local nimustine delivery rendezvousing with oral temozolomide chemotherapy in glioblastoma patients.

BACKGROUND: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery. METHODS: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded. RESULTS: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process. CONCLUSIONS: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities.