A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead

Clin Gastroenterol Hepatol. 2007 Sep;5(9):1100-8. doi: 10.1016/j.cgh.2007.04.021. Epub 2007 Jul 12.

Abstract

Background & aims: To assess the safety and efficacy of transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEB) for hepatocellular carcinoma (HCC).

Methods: Patients with incurable HCC and Child-Pugh class A cirrhosis were considered eligible for this phase I/II trial. Two courses of TACE using DEB were given at an interval of 2 months, and tumor response was assessed by computerized tomography scan. The phase I trial was a dose-escalating study starting from 25 mg to 150 mg doxorubicin in cohorts of 3 patients. The 150-mg doxorubicin dose was used for the phase II study. Primary end points were treatment-related complications and deaths. Secondary end points included tumor response and pharmacokinetics of doxorubicin.

Results: In the phase I study involving 15 patients, no dose-limiting toxicity was observed for up to 150 mg doxorubicin, which was used for 20 patients in the phase II study. The pharmacokinetic study showed a low peak plasma doxorubicin concentration (49.4 +/- 23.7 ng/mL), and no systemic toxicity was observed. The treatment-related complication rate was 11.4%. There was no treatment-related death. Among 30 patients who completed 2 courses of TACE, the partial response rate and the complete response rates were 50% and 0%, respectively, by response evaluation criteria in solid tumors (RECIST) criteria at computerized tomography scan 1 month after the second TACE. By modified RECIST criteria, taking into account the extent of tumor necrosis, 19 (63.3%) patients had a partial response and 2 (6.7%) had a complete response.

Conclusions: This study shows that TACE using DEB is a safe and effective treatment for HCC, supporting a phase III randomized trial to compare this novel treatment with conventional TACE using doxorubicin-Lipiodol emulsion.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiography
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / drug therapy*
  • Chemoembolization, Therapeutic / methods*
  • Chromatography, High Pressure Liquid
  • Contrast Media / administration & dosage
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Hepatic Artery
  • Humans
  • Injections, Intra-Arterial
  • Iodized Oil / administration & dosage
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / drug therapy*
  • Male
  • Microspheres*
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Contrast Media
  • Drug Combinations
  • Iodized Oil
  • Doxorubicin