AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
{{expandStatus?'Exit ':''}}Advanced Search
This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase Ⅰ trial.
A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.
The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t1/2 of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day.
This phase Ⅰ study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.
Ohgaki H. Epidemiology of brain tumors. Methods Mol Biol. 2009; 472: 323-42.
Rasmussen BK, Hansen S, Laursen RJ, Kosteljanetz M, Schultz H, Norgard BM, et al. Epidemiology of glioma: clinical characteristics, symptoms, and predictors of glioma patients grade Ⅰ-Ⅳ in the Danish Neuro-Oncology Registry. J Neurooncol. 2017; 135: 571-9.
Diwanji TP, Engelman A, Snider JW, Mohindra P. Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. Adolesc Health Med Ther. 2017; 8: 99-113.
Gallego O. Nonsurgical treatment of recurrent glioblastoma. Curr Oncol. 2015; 22: e273-81.
Li SY, Chang CQ, Ma FY, Yu CL. Modulating effects of chlorogenic acid on lipids and glucose metabolism and expression of hepatic peroxisome proliferator-activated receptor-alpha in golden hamsters fed on high fat diet. Biomed Environ Sci. 2009; 22: 122-9.
Xu R, Kang Q, Ren J, Li Z, Xu X. Antitumor molecular mechanism of chlorogenic acid on inducting genes GSK-3β and APC and inhibiting gene β-Catenin. J Anal Methods Chem. 2013; 2013: 951319.
Bandyopadhyay G, Biswas T, Roy KC, Mandal S, Mandal C, Pal BC, et al. Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells. Blood. 2004; 104: 2514-22.
Xue N, Zhou Q, Ji M, Jin J, Lai F, Chen J, et al. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype. Sci Rep. 2017; 7: 39011.
Jin UH, Lee JY, Kang SK, Kim JK, Park WH, Kim JG, et al. A phenolic compound, 5-caffeoylquinic acid (chlorogenic acid), is a new type and strong matrix metalloproteinase-9 inhibitor: isolation and identification from methanol extract of Euonymus alatus. Life Sci. 2005; 77: 2760-9.
Wu J, Chen H, Li H, Tang Y, Yang L, Cao S, et al. Antidepressant potential of chlorogenic acid-enriched extract from Eucommia ulmoides Oliver Bark with neuron protection and promotion of serotonin release through enhancing synapsin Ⅰ expression. Molecules. 2016; 21: 260.
Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010; 28: 1963-72.
Galanis E, Jaeckle KA, Maurer MJ, Reid JM, Ames MM, Hardwick JS, et al. Phase Ⅱ trial of vorinostat in recurrent glioblastoma multiforme: a north central cancer treatment group study. J Clin Oncol. 2009; 27: 2052-8.
van Linde ME, Brahm CG, de Witt Hamer PC, Reijneveld JC, Bruynzeel AME, Vandertop WP, et al. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol. 2017; 135: 183-92.
Wu HZ, Luo J, Yin YX, Wei Q. Effects of chlorogenic acid, an active compound activating calcineurin, purified from Flos Lonicerae on macrophage. Acta Pharmacol Sin. 2004; 25: 1685-9.
Park JJ, Hwang SJ, Park JH, Lee HJ. Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1alpha/AKT pathway. Cell Oncol (Dordr). 2015; 38: 111-8.
Wick A, Pascher C, Wick W, Jauch T, Weller M, Bogdahn U, et al. Rechallenge with temozolomide in patients with recurrent gliomas. J Neurol. 2009; 256: 734-41.
Creative Commons Attribution-NonCommercial 4.0 International License
京公网安备11010802044758号