Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics

J Hepatol. 2007 Mar;46(3):474-81. doi: 10.1016/j.jhep.2006.10.020. Epub 2006 Nov 29.

Abstract

Background/aims: This study assesses the safety, pharmacokinetics and efficacy of transarterial chemoembolization using drug eluting beads (DEB), an embolizing device that slowly releases chemotherapy to decrease systemic toxicity.

Methods: Twenty-seven Child-Pugh A cirrhotics (76% male, 59% HCV) with untreated large/multifocal HCC received chemoembolization with doxorubicin loaded DEBs at doses adjusted for bilirubin and body surface (range: 47-150 mg). Clinical and analytical data were recorded at 24 and 48 h, 7, 14 and 30 days after first and second TACE. Response rate was assessed by CT at 6 months. Blood samples were obtained in 13 patients at 5, 20, 40, 60, 120 min, 6, 24, 48 and 168 h to determine doxorubicin Cmax and AUC.

Results: DEB-TACE was well tolerated with an acceptable safety profile. Two cases developed liver abscess, one leading to death. Response rate was 75% (66.6% on intention-to-treat). Doxorubicin Cmax and AUC were significantly lower in DEB-TACE patients (78.97+/-38.3 ng/mL and 662.6+/-417.6 ng/mLmin) than in conventional TACE (2341.5+/-3951.9 ng/mL and 1812.2+/-1093.7 ng/mLmin, p=0.00002 and p=0.001, respectively). After a median follow-up of 27.6 months, 1- and 2-year survival is 92.5% and 88.9%, respectively.

Conclusions: Chemoembolization using DEBs is an effective procedure with a favorable pharmacokinetic profile.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacokinetics*
  • Area Under Curve
  • Carcinoma, Hepatocellular / drug therapy*
  • Chemoembolization, Therapeutic / adverse effects
  • Chemoembolization, Therapeutic / methods*
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics*
  • Drug Delivery Systems
  • Endpoint Determination
  • Female
  • Humans
  • Injections, Intra-Arterial
  • Liver Neoplasms / drug therapy*
  • Male
  • Microspheres*
  • Middle Aged
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin