title: A phase II study of halichondrin B analog eribulin mesylate (E7389) in patients with advanced non-small cell lung cancer previously treated with a taxane: a California cancer consortium trial.
abstract: BACKGROUND
  Eribulin mesylate (E7389) is an analog of halichondrin B with a unique mechanism of microtubule binding. The activity and toxicity of eribulin were assessed in patients with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane.
  
  
  METHODS
  An open-label phase II study included patients with NSCLC previously treated with platinum and taxane-based therapy, with up to two prior cytotoxic regimens, given for metastatic disease or as adjuvant therapy. Patients were stratified by taxane-sensitivity: taxane-sensitive (TS, progression >90 days after taxane) or taxane-resistant (TR, progression ≤90 days after taxane). Patients received an intravenous infusion of eribulin at 1.4 mg/m on days 1 and 8 every 21 days. The primary end point was objective response rate and secondary end points included progression-free survival and overall survival.
  
  
  RESULTS
  Sixty-six patients were accrued. The objective response rate was 5% with a median duration of response of 7.8 months. In the TS arm, 3 of 45 patients (7%) achieved a partial response and another 11 of 45 (24%) achieved stable disease for at least 3 months, whereas in the TR arm, no patients achieved a partial response and 4 of 21 (19%) achieved stable disease for at least 3 months. Median progression-free survival was 2.9 months in the TS subgroup and 1.2 months in the TR subgroup. The median overall survival was 12.6 months in the TS subgroup and 8.9 months in the TR subgroup. Toxicities were primarily hematologic; only two patients developed grade 3 neuropathy.
  
  
  CONCLUSIONS
  Eribulin mesylate is well tolerated and demonstrates activity in pretreated, TS NSCLC.
authors.affiliation: University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA. gitlitz@usc.edu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Gitlitz
authors.forename: Denice D
authors.initials: DD
authors.lastname: Tsao-Wei
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Angela
authors.initials: A
authors.lastname: Davies
authors.forename: Marianna
authors.initials: M
authors.lastname: Koczywas
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: Suresh
authors.initials: S
authors.lastname: Ramalingam
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Martin
authors.initials: M
authors.lastname: Edelman
authors.forename: Philip
authors.initials: P
authors.lastname: Hoffman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ballas
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Liu
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D004988:Ethers, Cyclic / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D005663:Furans / Q000627:therapeutic use*; D006801:Humans; D007659:Ketones / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018942:Macrolides / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000095662:Polyether Polyketides
chemical_list: D001952:Bridged-Ring Compounds; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; D010984:Platinum; D043823:Taxoids; C080625:taxane; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin