title: Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial.
abstract: BACKGROUND
  A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC).
  
  
  OBJECTIVE
  To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life.
  
  
  METHODS
  Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300-500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients.
  
  
  RESULTS
  Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months--not reached); the median overall survival was 24.5 months (95% CI 14.7 months--not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly.
  
  
  CONCLUSIONS
  Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559).
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France; Department of Pharmacy, University Hospital, Dijon, France.
authors.forename: M
authors.initials: M
authors.lastname: Boulin
authors.forename: P
authors.initials: P
authors.lastname: Hillon
authors.forename: J P
authors.initials: JP
authors.lastname: Cercueil
authors.forename: F
authors.initials: F
authors.lastname: Bonnetain
authors.forename: S
authors.initials: S
authors.lastname: Dabakuyo
authors.forename: A
authors.initials: A
authors.lastname: Minello
authors.forename: J L
authors.initials: JL
authors.lastname: Jouve
authors.forename: C
authors.initials: C
authors.lastname: Lepage
authors.forename: M
authors.initials: M
authors.lastname: Bardou
authors.forename: M
authors.initials: M
authors.lastname: Wendremaire
authors.forename: P
authors.initials: P
authors.lastname: Guerard
authors.forename: A
authors.initials: A
authors.lastname: Denys
authors.forename: A
authors.initials: A
authors.lastname: Grandvuillemin
authors.forename: B
authors.initials: B
authors.lastname: Chauffert
authors.forename: L
authors.initials: L
authors.lastname: Bedenne
authors.forename: B
authors.initials: B
authors.lastname: Guiu
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011788:Quality of Life; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D015255:Idarubicin