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  • Intratumoral bioavailability and specific effects in Phosphoethanolamin-MRI of the solubilised natural compound curcumin in glioblastoma patients

    Final Number:
    1088

    Authors:
    Stephan Dützmann MD; Christina Schiborr; Alexa Kocher; Elke Hattingen MD; Jakob Weissenberger; Florian Geßler MD; Johanna Quick MD; Kea Franz MD; Volker Seifert MD, PhD; Jan Frank PhD; Christian Senft MD, PhD

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: Curcumin is intensely investigated in numerous cancer types as a potential natural antitumoral agent. We previously reported on the anti-proliferative, anti-migratory and anti-invasive properties of the natural, nontoxic compound curcumin on glioblastoma cell lines and mouse models. In this prospective clinical trial in glioblastoma patients we sought to determine the intratumoral concentrations and clinical tolerance of solubilised curcumin and detect subtle changes in pioneering Phosphorus MR spectroscopic imaging(31P MRSI)to measure biological phosphate compounds. To enhance the bioavailability of curcumin we used an innovative liquid solution (“solubilisate”) with a colloidal micelle-like structure creating an ultrafine distribution of curcumin that can be taken as a beverage.

    Methods: In this prospective trial, thirteen patients scheduled for surgery of suspected newly diagnosed glioblastoma drank four days before surgery 1g of solubilised curcumin in a 200mL beverage of pear-juice three times per day after regular meals. Furthermore,before and after the period of intake,a 31P MRSI was performed to detect subtle changes in the tumoral metabolism.The concentration of total curcumin was analysed in tissue and blood samples using High Performance Liquid Chromatography.

    Results: Three patients discontinued the study because of nausea. They were excluded as well as one patient who developed pneumonia after drinking one beverage. In the remaining nine patients the mean intratumoral concentration of curcumin was 56 pg/mg of tissue (range 9-151).The mean serum concentration was 253 ng/mL (range 129-364). Inorganic phosphate showed a trend to increase within the tumor(p<0.1)as detected by 31P MRSI.The tumor volume of one patient decreased by 10% after ingestion of curcumin.All patients had stool softness because of the beverage.One patient developed a reversible skin rash.

    Conclusions: Here we report the highest serum concentration of curcumin detected in clinical studies so far. The trend toward an increase of inorganic phosphate within the tumor(p<0.1)might be due to curcumin-induced damage to mitochondrial pathways.Further studies are needed to determine its specific effects and the molecular profiles of patients that might benefit from oral ingestion of this natural compound.

    Patient Care: Develop novel readily available therapies in the treatment of glioblastoma.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of curcumin as a potential natural therapeutic in glioblastoma 2) Discuss, in small groups the relevance of changes in Phosphoethanolamin-MRI in glioblastoma patients

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