Effect of Electroacupuncture Combined With Paclitaxel Clinical Efficacy of Patients With Recurrence of High-grade Glioma

Summary

Gliomas are the most common type of primary brain tumors, with surgery followed by radiotherapy and chemotherapy as the main treatment modalities. However, they are highly prone to recurrence, presenting significant treatment challenges, especially for high-grade gliomas, which have a 5-year survival rate of only 5.5%. Paclitaxel, a common chemotherapeutic agent, exhibits antitumor effects in vitro that are 1400 times stronger than those of temozolomide (the first-line chemotherapy drug for gliomas). However, due to its large molecular weight (approximately 893 Da), it cannot cross the blood-brain barrier, precluding its use as a first-line treatment for gliomas. Preliminary research by our team has demonstrated that Specific Mode Electroacupuncture Stimulation (SMES) can open the blood-brain barrier, enhancing the concentration of albumin-bound paclitaxel (ABX) in tumor tissues, peritumoral tissues, and surrounding invasive tissues, thereby exerting antitumor effects. Consequently, this study aims to observe the safety and efficacy of SMES combined with ABX in treating patients with recurrent high-grade gliomas postoperatively, to explore its mechanisms of action, extend survival, improve quality of life, and forge new theories and methods for the integrative treatment of brain tumors combining traditional Chinese and Western medicine.

Timeline

Start

2024-04-01

Primary completion

2026-12-31

Completion

2027-12-31

Publications

• Results Weller M, Wick W, Aldape K, Brada M, Berger M, Pfister SM, Nishikawa R, Rosenthal M, Wen PY, Stupp R, Reifenberger G. Glioma. Nat Rev Dis Primers. 2015 Jul 16;1:15017. doi: 10.1038/nrdp.2015.17.
• Results Rapp M, Baernreuther J, Turowski B, Steiger HJ, Sabel M, Kamp MA. Recurrence Pattern Analysis of Primary Glioblastoma. World Neurosurg. 2017 Jul;103:733-740. doi: 10.1016/j.wneu.2017.04.053. Epub 2017 Apr 19.
• Results Wick W, Stupp R, Beule AC, Bromberg J, Wick A, Ernemann U, Platten M, Marosi C, Mason WP, van den Bent M, Weller M, Rorden C, Karnath HO; European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada Clinical Trials Group. A novel tool to analyze MRI recurrence patterns in glioblastoma. Neuro Oncol. 2008 Dec;10(6):1019-24. doi: 10.1215/15228517-2008-058. Epub 2008 Jul 31.
• Results Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9.
• Results Dmello C, Sonabend A, Arrieta VA, Zhang DY, Kanojia D, Chen L, Gould A, Zhang J, Kang SJ, Winter J, Horbinski C, Amidei C, Gyorffy B, Cordero A, Chang CL, Castro B, Hsu P, Ahmed AU, Lesniak MS, Stupp R, Sonabend AM. Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma. Clin Cancer Res. 2022 Jul 15;28(14):3156-3169. doi: 10.1158/1078-0432.CCR-21-2563.
• Results Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, Jones DTW, Joyce JA, Kearns P, Kieran MW, Mellinghoff IK, Merchant M, Pfister SM, Pollard SM, Ramaswamy V, Rich JN, Robinson GW, Rowitch DH, Sampson JH, Taylor MD, Workman P, Gilbertson RJ. Challenges to curing primary brain tumours. Nat Rev Clin Oncol. 2019 Aug;16(8):509-520. doi: 10.1038/s41571-019-0177-5.
• Results Terstappen GC, Meyer AH, Bell RD, Zhang W. Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021 May;20(5):362-383. doi: 10.1038/s41573-021-00139-y. Epub 2021 Mar 1.
• Results Parrish KE, Sarkaria JN, Elmquist WF. Improving drug delivery to primary and metastatic brain tumors: strategies to overcome the blood-brain barrier. Clin Pharmacol Ther. 2015 Apr;97(4):336-46. doi: 10.1002/cpt.71. Epub 2015 Feb 18.
• Results Cardoso FL, Brites D, Brito MA. Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev. 2010 Sep 24;64(2):328-63. doi: 10.1016/j.brainresrev.2010.05.003. Epub 2010 May 26.
• Results Agarwal S, Sane R, Oberoi R, Ohlfest JR, Elmquist WF. Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain. Expert Rev Mol Med. 2011 May 13;13:e17. doi: 10.1017/S1462399411001888.
• Results Fowler MJ, Cotter JD, Knight BE, Sevick-Muraca EM, Sandberg DI, Sirianni RW. Intrathecal drug delivery in the era of nanomedicine. Adv Drug Deliv Rev. 2020;165-166:77-95. doi: 10.1016/j.addr.2020.02.006. Epub 2020 Mar 3.
• Results Malani R, Fleisher M, Kumthekar P, Lin X, Omuro A, Groves MD, Lin NU, Melisko M, Lassman AB, Jeyapalan S, Seidman A, Skakodub A, Boire A, DeAngelis LM, Rosenblum M, Raizer J, Pentsova E. Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer. J Neurooncol. 2020 Jul;148(3):599-606. doi: 10.1007/s11060-020-03555-z. Epub 2020 Jun 6.
• Results Zagouri F, Zoumpourlis P, Le Rhun E, Bartsch R, Zografos E, Apostolidou K, Dimopoulos MA, Preusser M. Intrathecal administration of anti-HER2 treatment for the treatment of meningeal carcinomatosis in breast cancer: A metanalysis with meta-regression. Cancer Treat Rev. 2020 Aug;88:102046. doi: 10.1016/j.ctrv.2020.102046. Epub 2020 Jun 3.
• Results Tosi U, Kommidi H, Adeuyan O, Guo H, Maachani UB, Chen N, Su T, Zhang G, Pisapia DJ, Dahmane N, Ting R, Souweidane MM. PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models. Sci Adv. 2020 Jul 24;6(30):eabb4105. doi: 10.1126/sciadv.abb4105. eCollection 2020 Jul.
• Results Graham-Gurysh EG, Murthy AB, Moore KM, Hingtgen SD, Bachelder EM, Ainslie KM. Synergistic drug combinations for a precision medicine approach to interstitial glioblastoma therapy. J Control Release. 2020 Jul 10;323:282-292. doi: 10.1016/j.jconrel.2020.04.028. Epub 2020 Apr 23.
• Results Siegal T, Rubinstein R, Bokstein F, Schwartz A, Lossos A, Shalom E, Chisin R, Gomori JM. In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans. J Neurosurg. 2000 Apr;92(4):599-605. doi: 10.3171/jns.2000.92.4.0599.
• Results Park J, Aryal M, Vykhodtseva N, Zhang YZ, McDannold N. Evaluation of permeability, doxorubicin delivery, and drug retention in a rat brain tumor model after ultrasound-induced blood-tumor barrier disruption. J Control Release. 2017 Mar 28;250:77-85. doi: 10.1016/j.jconrel.2016.10.011. Epub 2016 Oct 11.
• Results Chen Zhongjian, Zhang Yuan, Zheng Yejiao, Yang Haiyan, Gu Liqiang. Research Progress on Borneol Promoting Drug Permeation Through the Blood-Brain Barrier [J]. Chinese Traditional Patent Medicine, 2019, 41(09): 2170-2173.
• Results Guo Junqia, Zhang Rong, Duan Meimei, Xing Yanmei. The Effect of Natural Borneol on the Permeability of MTX Through the Blood-Tumor Barrier [J]. Traditional Chinese Drug Research & Clinical Pharmacology, 2015, 26(01): 73-77.
• Results Zhang S, Gong P, Zhang J, Mao X, Zhao Y, Wang H, Gan L, Lin X. Specific Frequency Electroacupuncture Stimulation Transiently Enhances the Permeability of the Blood-Brain Barrier and Induces Tight Junction Changes. Front Neurosci. 2020 Oct 6;14:582324. doi: 10.3389/fnins.2020.582324. eCollection 2020.
• Results Caffery B, Lee JS, Alexander-Bryant AA. Vectors for Glioblastoma Gene Therapy: Viral & Non-Viral Delivery Strategies. Nanomaterials (Basel). 2019 Jan 16;9(1):105. doi: 10.3390/nano9010105.
• Results Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehar J, Kryukov GV, Sonkin D, Reddy A, Liu M, Murray L, Berger MF, Monahan JE, Morais P, Meltzer J, Korejwa A, Jane-Valbuena J, Mapa FA, Thibault J, Bric-Furlong E, Raman P, Shipway A, Engels IH, Cheng J, Yu GK, Yu J, Aspesi P Jr, de Silva M, Jagtap K, Jones MD, Wang L, Hatton C, Palescandolo E, Gupta S, Mahan S, Sougnez C, Onofrio RC, Liefeld T, MacConaill L, Winckler W, Reich M, Li N, Mesirov JP, Gabriel SB, Getz G, Ardlie K, Chan V, Myer VE, Weber BL, Porter J, Warmuth M, Finan P, Harris JL, Meyerson M, Golub TR, Morrissey MP, Sellers WR, Schlegel R, Garraway LA. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012 Mar 28;483(7391):603-7. doi: 10.1038/nature11003.
• Results Chang SM, Kuhn JG, Robins HI, Schold SC Jr, Spence AM, Berger MS, Mehta M, Pollack IF, Rankin C, Prados MD. A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American Brain Tumor Consortium report. Cancer. 2001 Jan 15;91(2):417-22. doi: 10.1002/1097-0142(20010115)91:23.0.co;2-9.
• Results Chamberlain MC, Kormanik P. Salvage chemotherapy with paclitaxel for recurrent primary brain tumors. J Clin Oncol. 1995 Aug;13(8):2066-71. doi: 10.1200/JCO.1995.13.8.2066.
• Results Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.
• Results Sonabend AM, Gould A, Amidei C, Ward R, Schmidt KA, Zhang DY, Gomez C, Bebawy JF, Liu BP, Bouchoux G, Desseaux C, Helenowski IB, Lukas RV, Dixit K, Kumthekar P, Arrieta VA, Lesniak MS, Carpentier A, Zhang H, Muzzio M, Canney M, Stupp R. Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial. Lancet Oncol. 2023 May;24(5):509-522. doi: 10.1016/S1470-2045(23)00112-2.

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