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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
  1. Amélie Anota1,2,
  2. Mathieu Boulin3,4,
  3. Sandrine Dabakuyo-Yonli1,5,
  4. Patrick Hillon3,6,
  5. Jean-Pierre Cercueil3,7,
  6. Anne Minello3,6,
  7. Jean-Louis Jouve3,6,
  8. Xavier Paoletti8,
  9. Laurent Bedenne3,6,
  10. Boris Guiu9,
  11. Franck Bonnetain1,2
  1. 1Quality of Life in Oncology National Platform, Besançon, France
  2. 2Methodological and Quality of Life in Oncology Unit (INSERM UMR 1098), University Hospital of Besançon, Besançon, France
  3. 3INSERM U866, University of Burgundy, Dijon, France
  4. 4Department of Pharmacy, University Hospital, Dijon, France
  5. 5Biostatistics and Quality of Life Unit (EA 4184), Centre Georges Francois Leclerc, Dijon, France
  6. 6Department of Hepatogastroenterology, University Hospital, Dijon, France
  7. 7Department of Interventional Radiology, University Hospital, Dijon, France
  8. 8Department of Biostatistics and Epidemiology, Institut Gustave Roussy, Paris, France
  9. 9Department of Radiology, St-Eloi University Hospital, Montpellier, France
  1. Correspondence to Amélie Anota; aanota{at}


Objectives 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).

Setting 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.

Participants Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21).

Primary and secondary outcome measurements 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.

Results 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)).

Conclusions 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.

Trial registration number NCT01040559; Post-results.

  • Health-related Quality of Life
  • oncology clinical trial
  • phase I
  • longitudinal analysis
  • time to deterioration

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