title: Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes.
abstract: BACKGROUND
  Eribulin inhibits microtubule dynamics via a mechanism distinct from that of other tubulin-targeting drugs, inducing cell-cycle arrest and tumour regression in preclinical models. We assessed the activity and safety of eribulin in four strata of patients with different types of soft-tissue sarcoma.
  
  
  METHODS
  In this non-randomised multicentre phase 2 study, patients were included if they had progressive or high-grade soft-tissue sarcoma and had received no more than one previous combination chemotherapy or up to two single drugs for advanced disease. They were stratified by the type of soft-tissue sarcoma they had. Eribulin was given intravenously at a concentration of 1·4 mg/m(2) over 2-5 min at days 1 and 8 every 3 weeks to primarily assess progression-free survival at 12 weeks (RECIST 1.0), which we evaluated in all patients who started treatment. Safety analyses were done in all patients who started treatment. This trial is registered at ClinicalTrials.gov, number NCT00413192.
  
  
  RESULTS
  Of 128 patients included, 37 had adipocytic sarcoma, 40 had leiomyosarcoma, 19 had synovial sarcoma, and 32 had other sarcomas. 12 (31·6%) of 38 patients with leiomyosarcoma evaluable for the primary endpoint, 15 (46·9%) of 32 patients with adipocytic sarcoma, four (21·1%) of 19 with synovial sarcoma, and five (19·2%) of 26 in other sarcomas were progression-free at 12 weeks. The most common grade 3-4 adverse events were neutropenia (66 [52%] of 127 patients evaluable for safety), leucopenia (44 [35%]), anaemia (nine [7%]), fatigue (nine [7%]), febrile neutropenia (eight [6%]), abnormal alanine aminotransferase concentrations (six [5%]), mucositis (four [3%]), and sensory neuropathy (four [3%]).
  
  
  CONCLUSIONS
  Eribulin deserves further study in this setting, based on progression-free survival at 12 weeks in leiomyosarcoma and adipocytic sarcoma.
  
  
  BACKGROUND
  Eisai Limited, Hatfield, UK.
authors.affiliation: University Hospitals Leuven, Catholic University Leuven, Department of General Medical Oncology, Leuven Cancer Institute, Leuven, Belgium. patrick.schoffski@uzleuven.be
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Isabelle Laure
authors.initials: IL
authors.lastname: Ray-Coquard
authors.forename: Angela
authors.initials: A
authors.lastname: Cioffi
authors.forename: Nguyen Bin
authors.initials: NB
authors.lastname: Bui
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bauer
authors.forename: Joerg Thomas
authors.initials: JT
authors.lastname: Hartmann
authors.forename: Anders
authors.initials: A
authors.lastname: Krarup-Hansen
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Herlinde
authors.initials: H
authors.lastname: Dumez
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Axel
authors.initials: A
authors.lastname: Le Cesne
authors.forename: Jantien
authors.initials: J
authors.lastname: Wanders
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hayward
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Monia
authors.initials: M
authors.lastname: Ouali
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenberger
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D005663:Furans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007659:Ketones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008698:Mesylates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D013584:Sarcoma, Synovial / Q000188:drug therapy / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; D008698:Mesylates; C490954:eribulin; D000095662:Polyether Polyketides