title: Vorinostat in refractory soft tissue sarcomas - Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO).
abstract: New treatment options for patients with metastatic Soft Tissue Sarcoma are urgently needed. Preclinical studies suggested activity of vorinostat, a histone deacetylase inhibitor.
  
  
  
  A multi-centre, open-label, non-randomised phase II trial to investigate the efficacy and safety of vorinostat in patients with locally advanced or metastatic Soft Tissue Sarcoma failing 1st-line anthracycline-based chemotherapy was initiated. Patients were treated with vorinostat 400 mg po qd for 28 d followed by a treatment-free period of 7 d, representing a treatment cycle of 5 weeks. Restaging was performed every three cycles or at clinical progression.
  
  
  
  Between 06/10 and 09/13, 40 Soft Tissue Sarcoma patients were treated with vorinostat at seven participating centres. Patients had received 1 (n=8, 20%), 2 (n=10, 25%) or ≥3 (n=22, 55%) previous lines of chemotherapy. Best response after three cycles of treatment was stable disease (n=9, 23%). Median progression-free survival and overall survival were 3.2 and 12.3 months, respectively. Six patients showed long-lasting disease stabilisation for up to ten cycles. Statistical analyses failed to identify baseline predictive markers in this subgroup. Major toxicities (grade ≥III) included haematological toxicity (n=6, 15%) gastrointestinal disorders (n=5, 13%), fatigue (n=4, 10%), musculoskeletal pain (n=4, 10%), and pneumonia (n=2, 5%).
  
  
  
  In a heavily pre-treated patient population, objective response to vorinostat was low. However, a small subgroup of patients had long-lasting disease stabilisation. Further studies aiming to identify predictive markers for treatment response as well as exploration of combination regimens are warranted.
  
  
  
  NCT00918489 (ClinicalTrials.gov) EudraCT-number: 2008-008513-19.
authors.affiliation: Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: th_schmitt@gmx.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitt
authors.affiliation: Department of Internal Medicine 3, University Hospital Ulm, Albert-Einstein-Allee 29, 89081 Ulm, Germany. Electronic address: regine.mayer-steinacker@uniklinik-ulm.de.
authors.forename: Regine
authors.initials: R
authors.lastname: Mayer-Steinacker
authors.affiliation: Department of Internal Medicine 2, University Hospital Tübingen, Otfried-Müller-Str.10, 72076 Tübingen, Germany. Electronic address: frank.mayer@med.uni-tuebingen.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Gruenwald.Viktor@mh-hannover.de.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: Department of Hematology and Oncology, Marien Hospital Düsseldorf, Rochusstraße 2, 40479 Düsseldorf, Germany. Electronic address: mail@onkologie-duesseldorf.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schütte
authors.affiliation: Department of Internal Medicine 2, University Medical Center Schleswig-Holstein, Arnold-Heller-Straße 3, 24105 Kiel, Germany. Electronic address: medklinik2@franziskus.de.
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Hartmann
authors.affiliation: Interdisciplinary Tumor Center, Mannheim University Medical Center, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Bernd.Kasper@umm.de.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kasper
authors.affiliation: Coordination Center for Clinical Trials (KKS), Heidelberg University Hospital, Vossstraße 2, 69115 Heidelberg, Germany. Electronic address: johannes.huesing@med.uni-heidelberg.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hüsing
authors.affiliation: Coordination Center for Clinical Trials (KKS), Heidelberg University Hospital, Vossstraße 2, 69115 Heidelberg, Germany. Electronic address: jacek.hajda@med.uni-heidelberg.de.
authors.forename: Jacek
authors.initials: J
authors.lastname: Hajda
authors.affiliation: Coordination Center for Clinical Trials (KKS), Heidelberg University Hospital, Vossstraße 2, 69115 Heidelberg, Germany. Electronic address: gregor.ottawa@med.uni-heidelberg.de.
authors.forename: Gregor
authors.initials: G
authors.lastname: Ottawa
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany. Electronic address: gunhild.mechtersheimer@med.uni-heidelberg.de.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Mechtersheimer
authors.affiliation: Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: gerd.mikus@med.uni-heidelberg.de.
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.affiliation: Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: juergen.burhenne@med.uni-heidelberg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Burhenne
authors.affiliation: Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: lorenz.lehmann@med.uni-heidelberg.de.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Lehmann
authors.affiliation: Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: christoph.heilig@med.uni-heidelberg.de.
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Heilig
authors.affiliation: Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: anthony.ho@med.uni-heidelberg.de.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: gerlinde.egerer@med.uni-heidelberg.de.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005858:Germany; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000077337:Vorinostat; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat
keywords: Histone deacetylase-inhibition; Locally advanced; Metastatic; Soft Tissue Sarcoma; Vorinostat