title: Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy.
abstract: BACKGROUND
  Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure.
  
  
  METHODS
  Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate.
  
  
  RESULTS
  In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥ 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients.
  
  
  CONCLUSIONS
  Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.
authors: Drug Development Unit, Royal Marsden Hospital/Institute of Cancer Research, Sutton, UK. Electronic address: johann.de-bono@icr.ac.uk.
authors: J S
authors: JS
authors: de Bono
authors: Drug Development Unit, Royal Marsden Hospital/Institute of Cancer Research, Sutton, UK.
authors: L R
authors: LR
authors: Molife
authors: Texas Oncology, Houston; US Oncology, Houston, USA.
authors: G
authors: G
authors: Sonpavde
authors: Department of Medical Oncology, Santa Creu I Sant Pau Hospital, Barcelona.
authors: J P
authors: JP
authors: Maroto
authors: Department of Medical Oncology, Vall d'Hebron Hospital, Barcelona, Spain.
authors: E
authors: E
authors: Calvo
authors: US Oncology, Houston, USA; Ocala Oncology, Ocala.
authors: T H
authors: TH
authors: Cartwright
authors: Caris Life Sciences, Irving.
authors: D M
authors: DM
authors: Loesch
authors: Eisai Inc., Woodcliff Lake.
authors: K
authors: K
authors: Feit
authors: Genentech Inc., South San Francisco, USA.
authors: A
authors: A
authors: Das
authors: Eisai Inc., Woodcliff Lake.
authors: E A
authors: EA
authors: Zang
authors: Eisai Ltd, Hatfield, UK.
authors: J
authors: J
authors: Wanders
authors: Eisai Inc., Andover.
authors: S
authors: S
authors: Agoulnik
authors: Department of Medicine, Section of Medical Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, USA.
authors: D P
authors: DP
authors: Petrylak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D018579:Patient Selection; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D043823:Taxoids / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007659:Ketones; D043823:Taxoids; C490954:eribulin; D000095662:Polyether Polyketides