title: Phase Ib/II study of elisidepsin in metastatic or advanced gastroesophageal cancer (IMAGE trial).
abstract: OBJECTIVE
  To determine the recommended dose and antitumor activity of single-agent elisidepsin as a 24-h intravenous (i.v.) infusion fortnightly [biweekly, d1 and 15 every 4 weeks (q4wk); Arm A, dose-intensity strategy] or as a 3-h i.v. infusion weekly (d1, 8, 15 and 22 q4wk; Arm B, dose-density strategy) in adult patients with unresectable, locally advanced or metastatic pretreated esophageal, gastroesophageal junction and gastric cancer.
  
  
  METHODS
  Patients were randomized to one of two elisidepsin dosing schedules. Phase Ib starting doses were 8.0 mg flat dose (FD) in Arm A and 3.0 mg FD in Arm B. Phase II subsequently explored antitumor activity of both dosing schedules at the respective recommended doses.
  
  
  RESULTS
  Forty-four patients received elisidepsin: 12 in stage Ib and 32 in stage II. The recommended doses were defined as 10 mg FD (Arm A) and 3.75 mg FD (Arm B). Both schedules were well tolerated. Most adverse events were mild or moderate, reversible and predictable with no meaningful differences between schedules. The pharmacokinetic profiles of both schedules were similar to those reported previously in patients with solid tumors treated with a comparable dose. An interim analysis found tumor control in one patient receiving elisidepsin fortnightly, and in none given elisidepsin weekly; patient accrual was therefore discontinued due to lack of efficacy.
  
  
  CONCLUSIONS
  Both schedules at the recommended doses presented an acceptable safety profile, but lack of response means that we do not recommend further evaluation of single-agent elisidepsin as chemotherapy for unresectable, locally advanced or metastatic gastroesophageal cancer.
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, UK.
authors.forename: Russell
authors.initials: R
authors.lastname: Petty
authors.affiliation: St James University Hospital, Leeds, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Anthoney
authors.affiliation: Centre Hospitalier Universitaire Morvan, Brest, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Metges
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Alsina
authors.affiliation: Institut Paoli Calmettes, Marseille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gonçalves
authors.affiliation: The Beatson West of Scotland Cancer Centre, Glasgow, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brown
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.affiliation: Centre François Baclesse, Caen, France.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gunzer
authors.affiliation: PharmaMar Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Laus
authors.affiliation: PharmaMar Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Iglesias Dios
authors.affiliation: PharmaMar Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Miguel-Lillo
authors.affiliation: PharmaMar Clinical R&D, Colmenar Viejo, Madrid, Spain.
authors.forename: Patrick
authors.initials: P
authors.lastname: Bohan
authors.affiliation: Institut Català d'Oncologia (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. ramonsalazar@iconcologia.net.
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047630:Depsipeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C522358:elisidepsin
keywords: Elisidepsin; Esophageal cancer; Esophagogastric junction cancer; Gastric cancer; Gastroesophageal cancer; PM02734