Two Studies Look at Promising Therapies for Liver Cancer

[Guest guest]

Two Studies Look at Promising Therapies for Liver Cancer

By Liz Highleyman

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.

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.

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-derived growth 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 time to symptomatic

progression. Secondary outcomes included time to radiologic

progression and safety.

Results

• 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).

Results

• 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. "

7/25/08