Continuous administration of sorafenib in combination with transarterial chemoembolization in patients with hepatocellular carcinoma: results of a phase I study

Oncologist. 2010;15(11):1198-204. doi: 10.1634/theoncologist.2010-0180. Epub 2010 Oct 29.


Background and aim: It is unknown whether sorafenib can be combined with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma. This study assesses the safety and tolerability of a continuous regimen of sorafenib combined with TACE.

Methods: This was an open-label phase I study testing a continuous administration of sorafenib (dose escalation from 200 mg twice daily [bid] to 400 mg bid) starting 7 days prior to TACE with doxorubicin (50 mg).

Results: Twenty-one patients were screened and 14 received sorafenib combined with TACE. Because there were no dose-limiting toxicities in the first three patients who received sorafenib at a dose of 200 mg bid, subsequent patients received 400 mg bid. Twenty-seven procedures were performed (median, two per patient) and two local therapy-related severe adverse events occurred. The median duration of sorafenib therapy was 246 days (range, 14-547 days). Sorafenib-related adverse events of grade ≥3 were hand-foot skin reaction (n = 3), weight loss (n = 2), diarrhea (n = 1), abdominal pain (n = 1), and thrombocytopenia (n = 3). After treatment with sorafenib and TACE, there was a significant decrease in the concentration of plasma vascular endothelial growth factor (VEGF) from 93 ng/l to 67 ng/l.

Conclusions: Continuous administration of sorafenib at a dose of 400 mg bid combined with TACE was tolerable. The adverse event profile of this regimen was comparable with that of sorafenib monotherapy with the exception of thrombocytopenia, which may be more frequent. There were no increases in the circulating VEGF levels after TACE with this combined regimen. (Swiss Association for the Study of the Liver study number 25; trial identifier, NCT00478374).

Publication types

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

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Protocols
  • Benzenesulfonates / administration & dosage*
  • Benzenesulfonates / adverse effects
  • Benzenesulfonates / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / therapy*
  • Catheters, Indwelling
  • Chemoembolization, Therapeutic*
  • Combined Modality Therapy
  • Doxorubicin / therapeutic use
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / therapy*
  • Mitomycin / therapeutic use
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use
  • Sorafenib
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood


  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Vascular Endothelial Growth Factor A
  • Niacinamide
  • Mitomycin
  • Doxorubicin
  • Sorafenib

Associated data