Evaluation of safety parameters and changes in serum concentration in liver transplant recipients treated with doxorubicin during the anhepatic period

Shogo Kobayashi, Hiroshi Wada, Naoki Hama, Hirofumi Akita, Koichi Kawamoto, Hidetoshi Eguchi, Koji Umeshita, Yuichiro Doki, Masaki Mori, Hiroaki Nagano

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Abstract

Purpose: Because of the recurrence of hepatocellular carcinoma (HCC) at the graft after liver transplantation, circulating HCC cells may be present during the anhepatic period. Intravenous doxorubicin (DOX) is used during the anhepatic period to combat these cells; however, pharmacokinetics data have been poorly analyzed. This study aims to investigate DOX administration during the anhepatic period. Patients and methods: We administered 5 mg/m2 DOX immediately after liver removal and compared serum DOX concentrations at several intervals during the anhepatic period in patients who underwent liver transplantation because of liver cirrhosis and HCC (n = 3) and patients who underwent liver resection owing to HCC with portal vein tumor thrombi (n = 5). We also measured serum DOX concentrations and pharmacokinetic parameters in transplant patients that received 3-15 mg/m2 DOX (n = 3 per dose level). We evaluated transplant patients' adverse drug reactions and survival. Results: At 10 and 30 min after DOX administration, serum DOX concentrations were elevated two- to threefold in transplant patients versus resection patients. Dose escalation in transplant patients exhibited a prolonged T 1/2 in the one-compartment model and T 1/2 β in the two-compartment model, as well as a dose-dependent elevation of the area under the curve. No obvious adverse drug reactions were noted at 3-15 mg/m2 DOX. In transplant patients, 5-year recurrence-free survival was 68.8 %; overall survival was 100.0 %. Conclusion: During the anhepatic period, serum DOX concentrations were elevated two- to threefold, T 1/2 was prolonged dose dependently, and up to 15 mg/m2 DOX could be safely administered.

Original languageEnglish
Pages (from-to)1325-1333
Number of pages9
JournalCancer chemotherapy and pharmacology
Volume72
Issue number6
DOIs
Publication statusPublished - Dec 1 2013

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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