title: A phase II study of the halichondrin B analog eribulin mesylate in gemcitabine refractory advanced pancreatic cancer.
abstract: BACKGROUND
  Eribulin mesylate is a halichondrin B analog that inhibits microtubule dynamics. Pre-clinical studies have suggested anti-tumor activity in pancreatic cancer. This phase II study of eribulin in patients with advanced pancreatic cancer previously treated with gemcitabine was conducted by the Princess Margaret Hospital Phase II consortium.
  
  
  METHODS
  Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and previous treatment with gemcitabine. The study was a single arm phase II trial using a Simon 2-stage design. The primary endpoint was response rate, secondary endpoints included time to progression and overall survival.
  
  
  RESULTS
  Fifteen patients were enrolled, 14 received treatment, and 12 were evaluable for response. The median age was 61, and the majority of patients were ECOG performance status 1. Grade 3 or greater adverse events included neutropenia (29%), fatigue (14%), peripheral neuropathy (7%) and thrombosis (7%). There were no complete or partial responses and therefore the study was closed after the first stage. The best response was stable disease in 5/12 (42%) of patients. Of these five patients, three had stable disease for 9 months or greater. Median time to progression was 1.4 months, and median overall survival was 6.1 months.
  
  
  CONCLUSIONS
  Eribulin was well tolerated but did not result in any objective responses in gemcitabine refractory pancreatic cancer. However, several patients had prolonged stable disease, suggesting that further studies of eribulin in pancreatic cancer may be warranted.
authors.affiliation: University Health Network-Princess Margaret Hospital, Toronto, ON, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Renouf
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Tang
authors.forename: Pierre
authors.initials: P
authors.lastname: Major
authors.forename: Monika K
authors.initials: MK
authors.lastname: Krzyzanowska
authors.forename: Bindi
authors.initials: B
authors.lastname: Dhesy-Thind
authors.forename: John R
authors.initials: JR
authors.lastname: Goffin
authors.forename: David
authors.initials: D
authors.lastname: Hedley
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Doyle
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; 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; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D000093542:Gemcitabine; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; D050257:Tubulin Modulators; D000093542:Gemcitabine; C070519:halichondrin B; D000095662:Polyether Polyketides; C490954:eribulin