title: Efficacy and safety of Dexrazoxane (DRZ) in sarcoma patients receiving high cumulative doses of anthracycline therapy - a retrospective study including 32 patients.
abstract: Anthracyclines, as the most effective therapy, are the cornerstone of advanced stage sarcoma treatment. However, anthracyclines can also contribute to myocardial dysfunction and congestive heart failure, ultimately limiting the therapeutic potential of the drug. Coadministration of Dexrazoxane has been shown to effectively reduce cardiotoxicity, however primarily in patients suffering in diseases other than sarcoma.
  
  
  
  The aim of this retrospective analysis was to evaluate safety and efficacy of chemotherapy with high cumulative doses of anthracyclines in combination with Dexrazoxane. The medical charts of 32 patients treated in four institutions were analyzed. Reasons for coadministration were rechallenge, reaching the cumulative anthracycline dose and preexisting heart failure.
  
  
  
  The median age was 54 years [18-68 years]. The median cumulative anthracycline dose before adding DRZ was 450 mg/m(2) and after administration of last anthracycline containing therapy 750 mg/m(2). Either during treatment or follow up, 2/27 patients (7 %) without preexisting major cardiac findings developed anthracycline-induced cardiotoxicity. The median overall survival (OS) from start of the first anthracycline containing chemotherapy was 46 months and 17 months from the initial coadministration of DRZ. At rechallenge, the median progression free survival (PFS) with DRZ was 7 months. In continuous therapy, the median PFS was 13 months from beginning of chemotherapy and 9 months from the addition of DRZ.
  
  
  
  Chemotherapy with high cumulative doses of anthracyclines in addition with DRZ demonstrated a remarkable OS in these advanced disease patients. Cardiac side-effects due to high cumulative doses of anthracyclines requiring discontinuation of anthracycline treatment were rare. A PFS of 9 months from the beginning of the coadministration of DRZ indicates that continuing anthracycline therapy beyond established cumulative doses is a promising therapeutic option.
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany. Markus.Schuler@uniklinikum-dresden.de.|Department of Internal Medicine II, HELIOS Clinic Emil von Behring, Walterhöferstr. 11, 14165, Berlin, Germany. Markus.Schuler@uniklinikum-dresden.de.
authors: Markus K
authors: MK
authors: Schuler
authors: Institute of Medical Informatics and Biometry, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
authors: Sebastian
authors: S
authors: Gerdes
authors: Department of Hematology and Oncology, HELIOS Clinic Bad Saarow, Pieskower Straße 33, 15526, Bad Saarow, Germany.
authors: Antje
authors: A
authors: West
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
authors: Stephan
authors: S
authors: Richter
authors: Department of Internal Medicine C, University Hospital Greifswald, Sauerbruchstraße, 17475, Greifswald, Germany.
authors: Christoph
authors: C
authors: Busemann
authors: University Cancer Center, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
authors: Leopold
authors: L
authors: Hentschel
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
authors: Felicitas
authors: F
authors: Lenz
authors: Department of Internal Medicine II, University Hospital Tübingen, Eberhard Karls University Tübingen, Geissweg 3, 72076, Tübingen, Germany.
authors: Hans-Georg
authors: HG
authors: Kopp
authors: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.|University Cancer Center, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
authors: Gerhard
authors: G
authors: Ehninger
authors: Department of Interdisciplinary Oncology, HELIOS Clinic Berlin-Buch, Berlin, Germany.
authors: Peter
authors: P
authors: Reichardt
authors: Department of Hematology and Oncology, HELIOS Clinic Bad Saarow, Pieskower Straße 33, 15526, Bad Saarow, Germany.|Department of Internal Medicine C, University Hospital Greifswald, Sauerbruchstraße, 17475, Greifswald, Germany.
authors: Daniel
authors: D
authors: Pink
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D066126:Cardiotoxicity / Q000209:etiology / Q000517:prevention & control*; D064730:Dexrazoxane / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D016166:Free Radical Scavengers; D064730:Dexrazoxane
keywords: Advanced disease; Anthracyclines; Cardiotoxicity; Dexrazoxane; Palliative care; Soft tissue sarcoma