title: Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine.
abstract: OBJECTIVE
  The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine.
  
  
  METHODS
  Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) assessed by independent review.
  
  
  RESULTS
  Of 299 enrolled patients who had received a median of four prior chemotherapy regimens, 291 received eribulin (for a median of four cycles). Of these, 269 patients met key inclusion criteria for the primary efficacy analysis. The primary end point of ORR by independent review was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD > or = 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to 18.9%). Median duration of response was 4.1 months, and progression-free survival was 2.6 months. Median overall survival was 10.4 months. The most common treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4); grade 3 neuropathy occurred in 6.9% of patients (no grade 4).
  
  
  CONCLUSIONS
  Eribulin demonstrated antitumor activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine, with a manageable tolerability profile.
authors.affiliation: Vall d'Hebron University Hospital, Barcelona, Spain. jacortes@vhebron.net
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.forename: Linda
authors.initials: L
authors.lastname: Vahdat
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Blum
authors.forename: Chris
authors.initials: C
authors.lastname: Twelves
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Ahmad
authors.initials: A
authors.lastname: Awada
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Anthony
authors.initials: A
authors.lastname: Goncalves
authors.forename: Dale E
authors.initials: DE
authors.lastname: Shuster
authors.forename: Jantien
authors.initials: J
authors.lastname: Wanders
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Renuka
authors.initials: R
authors.lastname: Gurnani
authors.forename: Elaine
authors.initials: E
authors.lastname: Richmond
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Cole
authors.forename: Simon
authors.initials: S
authors.lastname: Ashworth
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Allison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004988:Ethers, Cyclic; D005260:Female; D005663:Furans / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000009:adverse effects / Q000627:therapeutic use*; D018942:Macrolides; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D019233:Retreatment; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin