title: An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma.
abstract: The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD).
  
  
  
  This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE.
  
  
  
  Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21).
  
  
  
  The primary objective was to determine the maximum tolerated dose (MTD) of idarubicin loaded after a single TACE session. MTD was defined as the dose level closest to that causing dose-limiting toxicity in 20% of patients. HRQoL was the secondary end point.
  
  
  
  Between March 2010 and March 2011, 9, 6 and 6 patients were included at idarubicin dose levels of 5, 10 and 15 mg, respectively. Calculated MTD of idarubicin was 10 mg. At the 10 mg idarubicin dose, patients presented a longer TTD than at 5 mg, for global health status (HR=0.91 (95% CI 0.18 to 4.72)), physical functioning (HR=0.38 (0.04 to 3.22)), fatigue (HR=0.67 (0.18 to 2.56)) and pain (HR=0.47 (0.05 to 4.24)).
  
  
  
  These HRQoL results were consistent with the estimated MTD, with a median TTD for global health status of 41 days (21 to NA) at 5 mg, 23 days (20 to NA) at 10 mg and 25 days (17 to NA) at 15 mg. These results show the importance of studying HRQoL in phase I trials.
  
  
  
  NCT01040559; Post-results.
authors.affiliation: Quality of Life in Oncology National Platform, Besançon, France Methodological and Quality of Life in Oncology Unit (INSERM UMR 1098), University Hospital of Besançon, Besançon, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Anota
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Pharmacy, University Hospital, Dijon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boulin
authors.affiliation: Quality of Life in Oncology National Platform, Besançon, France Biostatistics and Quality of Life Unit (EA 4184), Centre Georges Francois Leclerc, Dijon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dabakuyo-Yonli
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Hepatogastroenterology, University Hospital, Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hillon
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Interventional Radiology, University Hospital, Dijon, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cercueil
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Hepatogastroenterology, University Hospital, Dijon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Minello
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Hepatogastroenterology, University Hospital, Dijon, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Jouve
authors.affiliation: Department of Biostatistics and Epidemiology, Institut Gustave Roussy, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Paoletti
authors.affiliation: INSERM U866, University of Burgundy, Dijon, France Department of Hepatogastroenterology, University Hospital, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
authors.affiliation: Department of Radiology, St-Eloi University Hospital, Montpellier, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Guiu
authors.affiliation: Quality of Life in Oncology National Platform, Besançon, France Methodological and Quality of Life in Oncology Unit (INSERM UMR 1098), University Hospital of Besançon, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D016461:Chemoembolization, Therapeutic; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D011788:Quality of Life
chemical_list: D000903:Antibiotics, Antineoplastic; D015255:Idarubicin
keywords: Health-related Quality of Life; longitudinal analysis; oncology clinical trial; phase I; time to deterioration