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@ARTICLE{Knig:128929,
      author       = {M. König and C. von Hagens and S. Hoth and I. Baumann and
                      I. Walter-Sack and L. Edler$^*$ and S. Sertel},
      title        = {{I}nvestigation of ototoxicity of artesunate as add-on
                      therapy in patients with metastatic or locally advanced
                      breast cancer: new audiological results from a prospective,
                      open, uncontrolled, monocentric phase {I} study.},
      journal      = {Cancer chemotherapy and pharmacology},
      volume       = {77},
      number       = {2},
      issn         = {0344-5704},
      address      = {Berlin},
      publisher    = {Springer62507},
      reportid     = {DKFZ-2017-04941},
      pages        = {413-427},
      year         = {2016},
      abstract     = {Artesunate (ART) has been used for a long time in the
                      treatment of Plasmodium falciparum malaria and has been
                      considered safe. The present phase I study aimed to
                      determine the daily dose of ART that is well tolerated as
                      add-on therapy in patients with breast cancer for 4 weeks
                      of therapy. Ototoxicity could be a potential safety concern
                      in settings different from malaria. Therefore, comprehensive
                      audiological assessment was essential.The ARTIC M33/2 study
                      was a prospective, open, uncontrolled, monocentric phase I
                      dose-escalation study to evaluate the safety and
                      tolerability of ART in patients with advanced breast cancer.
                      Patients received either 100, 150 or 200 mg oral ART daily
                      for a test phase of 4 weeks as add-on therapy to their
                      ongoing oncological treatment. For the investigation of the
                      safety of ART for hearing, an audiological assessment was
                      performed with each patient before the intake of ART and
                      after 4 weeks of therapy.Twenty-three female patients were
                      included in the study. During the test phase, four patients
                      had adverse events (AEs) of the auditory system possibly
                      related to the intake of ART. However, none of these AEs was
                      classified as severe AE (SAE) and did not require treatment
                      interruption. Four patients had AEs concerning the
                      vestibular system (vertigo) during the test phase, one of
                      which was classified as SAE. However, the SAE was fully
                      reversible after discontinuation of ART.None of the
                      audiological results after 4 weeks of therapy with ART
                      showed any dose-limiting auditory toxicity. However,
                      audiological monitoring in further clinical studies with
                      prolonged use of oral ART in doses up to 200 mg daily is
                      warranted. The ARTIC M33/2 study is registered at
                      eudract.ema.europa.eu with the Number 2007-004432-23 and at
                      clinicaltrials.gov with the Number NCT00764036.},
      keywords     = {Antimalarials (NLM Chemicals) / Artemisinins (NLM
                      Chemicals) / artesunate (NLM Chemicals)},
      cin          = {C060},
      ddc          = {610},
      cid          = {I:(DE-He78)C060-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26793976},
      doi          = {10.1007/s00280-016-2960-7},
      url          = {https://inrepo02.dkfz.de/record/128929},
}