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

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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.

Sorafenib

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.

Results

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).

Results

“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.”

7/25/08

References

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.