Back HBV Disease Progression Liver Cancer/HCC Two Studies Look at Promising Therapies for Liver Cancer: Sorafenib and Doxorubicin

Two Studies Look at Promising Therapies for Liver Cancer: Sorafenib and Doxorubicin


Two recently published studies produced promising data on experimental therapies for HCC: the systemic chemotherapy drug sorafenib (Nexavar), and combination therapy using doxorubicin-eluting beads plus radiofrequency ablation.

Over years or decades, a proportion of people with chronic hepatitis B or C virus infection (HBV, HCV) will develop hepatocellular carcinoma (HCC), or primary liver cancer. Liver cancer is the third leading cause of cancer death worldwide, and in the U.S. rates are rising as people infected with HCV many years ago reach the later stages of disease.

Unfortunately, HCC is a difficult malignancy to treat, especially because it is often diagnosed late. However, recent years have witnessed several advances in treatment, and survival rates have improved.


In the July 24, 2008 New England Journal of Medicine, investigators reported data from the pivotal Phase III SHARP (Sorafenib HCC Assessment Randomized Protocol) trial.

Sorafenib is an oral multikinase inhibitor of vascular endothelial growth factor receptor, platelet-derivedgrowth factor receptor, and Raf. Already approved for primary kidney cancer, the U.S. Food and Drug Administration (FDA) approved sorafenib in November 2007 for treatment of unresectable (not curable by surgery) HCC, in part based on the SHARP results.

In this double-blind, multicenter trial, 602 participants with advanced HCC who had not undergone previous systemic treatment were randomly assigned to receive 400 mg twice-daily sorafenib or placebo. Primary outcomes were overall survival and timeto symptomatic progression. Secondary outcomes included time to radiologic progression and safety.


  • At the second planned interim analysis, 321 deaths had occurred, and the study was stopped ahead of schedule.
  • The median overall survival duration was 10.7 months in the sorafenib arm compared with 7.9 months in the placebo arm (hazard ratio 0.69; P < 0.001).
  • There was no significant difference between the 2 groups in the median time to symptomatic progression (4.1 vs 4.9 months, respectively; P = 0.77).
  • The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P < 0.001).
  • 7 patients in the sorafenib group (2%) and 2 in the placebo group (1%) experienced a partial response.
  • No participants in either group experienced a complete response.
  • Diarrhea, weight loss, hand/foot skin reaction, and hypophosphatemia (elevated blood phosphate) were more frequent in the sorafenib group.

Based on these findings, the investigators concluded, “In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.”

As previously reported, researchers presented data at the 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008) this past April showing that sorafenib also extended survival in a subgroup of more than 300 SHARP participants who experienced failure of prior local HCC therapies including resection (surgery), percutaneous ethanol injection, radiofrequency ablation, and/or transarterial chemoembolization.

Doxorubicin Beads + RF Ablation

Prior research has shown that a combination of different HCC therapies can produce better outcomes than single methods used alone.

As reported in the August 2008 Journal of Hepatology, Italian researchers assessed the safety and efficacy of doxorubicin-eluting beads (DEB) – tiny injected spheres that emit a chemotherapy drug – following radiofrequency (RF) ablation, a method of destroying tumors using heat.

The study included 20 patients with single HCC tumors ranging from 3.3 to 7.0 cm (mean 5.0 cm) who showed evidence of residual tumor tissue after standard RF ablation. The participants then underwent intra-arterial DEB administration equivalent to a doxorubicin dose of 50-125 mg (mean 60.2 mg). The follow-up period ranged from 6 to 20 months (mean 12 months).


  • The volume of treatment-induced necrosis (tissue death) measured by imaging increased from 48.1 cm3 after RF ablation to 75.5 cm3 after DEB administration.
  • This represented an increase of 60.9%.
  • The enhanced effect resulted in confirmed complete response of the target tumor in 12 of 20 patients (60%).
  • Incomplete response with persistence of < 10% of initial tumor volume was observed in 6 patients (30%).
  • Local tumor progression occurred in 2 patients (10%).
  • No major complications occurred, and no deterioration of liver function was observed.

“Intra-arterial DEB administration substantially enhances the effect of RF ablation,” the study authors concluded. “DEB-enhanced RF ablation is safe and results in a high rate of complete response in patients refractory to standard RF treatment.”



JM Llovet, S Ricci, V Mazzaferro, and others. Sorafenib in advanced hepatocellular carcinoma. New England Journal of Medicine 359(4): 378-390. July 24, 2008.

LR Roberts. Sorafenib in liver cancer -- just the beginning. New England Journal of Medicine 359(4): 420-422. July 24, 2008.

RLencioni, L Crocetti, P Petruzzi, and others. Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: A pilot clinical study. Journal of Hepatology 49(2): 217-222. August 2008.