Cornelia von Hagens1, Ingeborg Walter-Sack2, Maren Goeckenjan3,4, Julia Osburg3,5, Brigitte Storch-Hagenlocher6, Serkan Sertel7, Michael Elsässer8, Bjoern Andrew Remppis9,10, Lutz Edler11, Judith Munzinger12, Thomas Efferth13, Andreas Schneeweiss14, Thomas Strowitzki3. 1. Naturopathy and Integrative Medicine, Department of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. cornelia.von.hagens@med.uni-heidelberg.de. 2. Clinical Pharmacology and Pharmacoepidemiology, University Hospital, Heidelberg, Germany. 3. Naturopathy and Integrative Medicine, Department of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. 4. Department of Gynecology and Obstetrics, TU Dresden, Dresden, Germany. 5. Heidelberg School of Chinese Medicine, Heidelberg, Germany. 6. Neuro-Center, University Hospital, Heidelberg, Germany. 7. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Heidelberg, Germany. 8. University Women's Hospital, Heidelberg, Germany. 9. Department of Cardiology, University Hospital, Heidelberg, Germany. 10. Heart and Vascular Centre, Bad Bevensen, Germany. 11. Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany. 12. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. 13. Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany. 14. National Center for Tumor Diseases, University-Hospital, Heidelberg, Germany.
Abstract
PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy. METHODS: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According to the statistical design, recruitment was scheduled in groups of three patients in order not to miss a more than 33% frequency of dose-limiting adverse events (DL-AE) prior to dose escalation. RESULTS: Twenty-three patients were recruited, and all planned dose levels were applied. During the actual trial period of 4 ± 1 weeks, three patients experienced six DL-AEs altogether (leucopenia, neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any dose level). CONCLUSIONS: Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and well tolerated; therefore, 200 mg/d are recommended for phase II/III trials. Safety monitoring should include reticulocytes, NTproBNP, as well as audiological and neurological exploration.
PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancerpatients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy. METHODS:Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According to the statistical design, recruitment was scheduled in groups of three patients in order not to miss a more than 33% frequency of dose-limiting adverse events (DL-AE) prior to dose escalation. RESULTS: Twenty-three patients were recruited, and all planned dose levels were applied. During the actual trial period of 4 ± 1 weeks, three patients experienced six DL-AEs altogether (leucopenia, neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any dose level). CONCLUSIONS: Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and well tolerated; therefore, 200 mg/d are recommended for phase II/III trials. Safety monitoring should include reticulocytes, NTproBNP, as well as audiological and neurological exploration.
Authors: Suzy V Torti; David H Manz; Bibbin T Paul; Nicole Blanchette-Farra; Frank M Torti Journal: Annu Rev Nutr Date: 2018-08-21 Impact factor: 11.848
Authors: Tony Fröhlich; Anita Kiss; János Wölfling; Erzsébet Mernyák; Ágnes E Kulmány; Renáta Minorics; István Zupkó; Maria Leidenberger; Oliver Friedrich; Barbara Kappes; Friedrich Hahn; Manfred Marschall; Gyula Schneider; Svetlana B Tsogoeva Journal: ACS Med Chem Lett Date: 2018-10-19 Impact factor: 4.345
Authors: Lisa Gruber; Sara Abdelfatah; Tony Fröhlich; Christoph Reiter; Volker Klein; Svetlana B Tsogoeva; Thomas Efferth Journal: Molecules Date: 2018-04-06 Impact factor: 4.411