PMID- 26793976 OWN - NLM STAT- MEDLINE DCOM- 20160626 LR - 20181202 IS - 1432-0843 (Electronic) IS - 0344-5704 (Linking) VI - 77 IP - 2 DP - 2016 Feb TI - Investigation 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. PG - 413-27 LID - 10.1007/s00280-016-2960-7 [doi] AB - PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. FAU - Konig, Miriam AU - Konig M AD - Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. FAU - von Hagens, Cornelia AU - von Hagens C AD - Naturopathy and Integrative Medicine, Department of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Heidelberg, Germany. FAU - Hoth, Sebastian AU - Hoth S AD - Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. FAU - Baumann, Ingo AU - Baumann I AD - Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. FAU - Walter-Sack, Ingeborg AU - Walter-Sack I AD - Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital, Heidelberg, Germany. FAU - Edler, Lutz AU - Edler L AD - Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany. FAU - Sertel, Serkan AU - Sertel S AD - Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. serkan.sertel@med.uni-heidelberg.de. LA - eng SI - ClinicalTrials.gov/NCT00764036 SI - EudraCT/2007-004432-23 PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160121 PL - Germany TA - Cancer Chemother Pharmacol JT - Cancer chemotherapy and pharmacology JID - 7806519 RN - 0 (Antimalarials) RN - 0 (Artemisinins) RN - 60W3249T9M (Artesunate) SB - IM EIN - Cancer Chemother Pharmacol. 2016 Jun;77(6):1321. PMID: 27094900 MH - Adult MH - Antimalarials/administration & dosage/adverse effects/pharmacokinetics MH - *Artemisinins/administration & dosage/adverse effects/pharmacokinetics MH - Artesunate MH - Audiometry/methods MH - *Breast Neoplasms/drug therapy/pathology MH - Dose-Response Relationship, Drug MH - Drug Monitoring/methods MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Treatment Outcome MH - *Vertigo/chemically induced/diagnosis OTO - NOTNLM OT - Artesunate OT - Breast cancer OT - Metastasis OT - Ototoxicity EDAT- 2016/01/23 06:00 MHDA- 2016/06/28 06:00 CRDT- 2016/01/23 06:00 PHST- 2015/10/21 00:00 [received] PHST- 2016/01/05 00:00 [accepted] PHST- 2016/01/23 06:00 [entrez] PHST- 2016/01/23 06:00 [pubmed] PHST- 2016/06/28 06:00 [medline] AID - 10.1007/s00280-016-2960-7 [pii] AID - 10.1007/s00280-016-2960-7 [doi] PST - ppublish SO - Cancer Chemother Pharmacol. 2016 Feb;77(2):413-27. doi: 10.1007/s00280-016-2960-7. Epub 2016 Jan 21.