Preprint Concept Paper Version 1 This version is not peer-reviewed

Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen

Version 1 : Received: 29 October 2018 / Approved: 29 October 2018 / Online: 29 October 2018 (14:12:07 CET)

How to cite: Kast, R.; Skuli, N.; Sardi, I.; Capanni, F.; Hessling, M.; Frosina, G.; Kast, A.; Karpel-Massler, G.; Halatsch, M. Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen. Preprints 2018, 2018100689 (doi: 10.20944/preprints201810.0689.v1). Kast, R.; Skuli, N.; Sardi, I.; Capanni, F.; Hessling, M.; Frosina, G.; Kast, A.; Karpel-Massler, G.; Halatsch, M. Augmentation of 5-aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-fluorouracil and Febuxostat: The CAALA Regimen. Preprints 2018, 2018100689 (doi: 10.20944/preprints201810.0689.v1).

Abstract

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its selective conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently marketed drugs - the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat - that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

Subject Areas

5-aminolevulinic acid, ciprofloxacin, deferiprone, fluorescence, 5-fluorouracil, febuxostat, glioblastoma, photodynamic treatment, temozolomide,

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