title: Aplidin in patients with advanced dedifferentiated liposarcomas: a French Sarcoma Group Single-Arm Phase II study.
abstract: BACKGROUND
  Preclinical data have suggested a therapeutic role of JUN pathway activation in dedifferentiated liposarcoma (DDLPS) tumorigenesis. Aplidin is a drug inducing apoptosis through a strong, sustained activation of c-Jun NH2-terminal kinase.
  
  
  METHODS
  This phase II trial included patients with progressive advanced DDLPS. They received Aplidin 5 mg/m(2) days 1-15, 28-day cycle until disease progression or unacceptable toxicity. The primary end point was the 3-month nonprogression rate (PFS3) defined as the proportion of patients with nonprogressive disease at 3 months. A PFS3 of 40% considered as a reasonable objective to claim drug efficacy.
  
  
  RESULTS
  Between August 2012 and May 2013, 24 patients were included. Sixteen had received prior chemotherapy. Twenty-two were assessable for efficacy. The PFS3 was 9.1% [95% confidence interval (CI) 1.1-29.2]. Median progression-free and overall survivals were 1.6 months (95% CI 1.4-2.6) and 9.2 months (95% CI 6.6-). The most frequent adverse events of any grade were nausea, fatigue, anorexia, vomiting and diarrhea.
  
  
  CONCLUSIONS
  Aplidin did not meet the primary end point of this trial and do not deserve further investigation in DDLPS.
  
  
  BACKGROUND
  NCT01876043.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux.
authors.forename: M
authors.initials: M
authors.lastname: Toulmonde
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif.
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: Department of Medicine, Institut Curie, Paris.
authors.forename: S
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Department of Medicine, Centre Oscar Lambret, Lille.
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.affiliation: Department of Medicine, Institut Claudius Regaud, Toulouse.
authors.forename: C
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Department of Medical Oncology, Hôpital La Timone, Marseille.
authors.forename: F
authors.initials: F
authors.lastname: Duffaud
authors.affiliation: Clinical and Epidemiological Research Unit, Institut Bergonié, Bordeaux Data Center for Cancer Clinical Trials, CTD-INCa, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Bellera
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux a.italiano@bordeaux.unicancer.fr.
authors.forename: A
authors.initials: A
authors.lastname: Italiano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D047630:Depsipeptides / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008080:Liposarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010456:Peptides, Cyclic; D011379:Prognosis; D015996:Survival Rate
chemical_list: D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin
keywords: Aplidin; JUN; dedifferentiated liposarcoma; plitidepsin; treatment