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中华神经外科疾病研究杂志 2018年第4期17卷 375-375页

作者： Desjardins A gromeier M Herndon JE 2nd Beaubier N Bolognesi DP Friedman AH Friedman HS McSherry F Muscat AM Nair S Peters KB Randazzo D Sampson JH vlahovic g Harrison WT McLendon RE Ashley D Bigner DD

Background The prognosis of patients with recurrent World Health Organization(WHO)grade IV malignant glioma is dismal,and there is currently no effective *** conducted a dose-finding and toxicity study in this population of patients,evaluating convection-enhanced,intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera(PVSRIPO).PVSRIPO recognizes the poliovirus receptor CD155,which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor *** We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma,confirmed on histopathological testing,with measurable disease(contrast-enhancing tumor of≥1 cm and≤5.5 cm in the greatest dimension).The study evaluated seven doses,ranging between 107 and 1010 50%tissue-culture infectious doses(TCID50),first in a dose-escalation phase and then in a dose-expansion *** From May 2012 through May 2017,a total of 61 patients were enrolled and received a dose of *** level-1(5.0×107TCID50)was identified as the phase 2 *** dose-limiting toxic effect was observed;a patient in whom dose level 5(1010TCID50)was administered had a grade 4 intracranial hemorrhage immediately after the catheter was *** mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use,dose level 5 was deescalated to reach the phase 2 *** the dose-expansion phase,19%of the patients had a PVSRIPO-related adverse event of grade 3 or *** survival among the patients who received PVSRIPO reached a plateau of 21%(95%confidence interval,11 to 33)at 24 months that was sustained at 36 *** Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent *** survival rate among patients who receivedPVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls.

关键词： WHO

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