Sorafenib offers hope in the battle for liver cancer survival
The outlook for hepatocellular carcinoma (HCC) sufferers is bleak - current medication has a five-year survival rate for those with liver cancer of less than 5% in the developed world and even lower in developing countries. However, patients in trials of a new drug called Sorafenib have seen their survival times double. Datamonitor's Dr Lorna Fern investigates...

Liver cancer is currently the fifth most common cancer in the world, responsible for about one million cases and half a million deaths globally every year. HCC is a tumor of the liver that arises from focal scarring points in cirrhotic liver tissue, and its global incidence is on the increase, concurrent with a global increase in the number of cases of viral hepatitis and of alcoholic cirrhosis in developed countries.

Some specialists have described it as a 'waiting epidemic'. In the US alone there has been a three-fold increase in the incidence of HCC over the last decade. Similar trends have been seen in four other pharmaceutical markets including the United Kingdom, France and Canada.

Bleak outlook

Furthermore, opinion leaders predict that the full effect of hepatitis B (HBV) vaccination programs will not be felt for another 10-15 years. There is no hepatitis C (HCV) vaccine and the effect of blood screening programs introduced in the 1990s will not curb the rising incidence of HCV-related HCC for at least two decades.

The effects of binge drinking on the increasing incidence of HCC remains to be seen. However, today's binge drinking culture has already been linked to an increase in liver cirrhosis in developed countries, and thus may in turn increase the numbers of HCC cases. Studies have found that liver cirrhosis is becoming a major public health concern in the UK, and it is affecting men and women at younger ages than ever seen before. Datamonitor predicts the incidence of HCC will continue to increase resulting in a large, clinically underserved patient population.

The treatment of liver cancer presents a formidable challenge to physicians as it frequently presents in the setting of liver cirrhosis. HCC is often described as two diseases in one - a virulent malignant disorder arising in the setting of chronic liver disease. Between 70-90% of HCC patients will have liver cirrhosis at the time of diagnosis.

The problem in patients with liver cirrhosis is that the cirrhosis itself severely compromises liver function. This increases the toxicity of anticancer drugs as the pivotal role that the liver plays in their detoxification and removal is diminished. Indeed it is often the condition of the remaining liver that dictates the final treatment options.

HCC patients not only require effective agents to treat the tumor, but there is also significant unmet need for drugs that will stabilize and treat the underlying liver disease. Surgical resection of the primary tumor or liver transplantation are the only potentially curative options for HCC patients. However, because it is complicated by underlying liver cirrhosis, only 10% of patients are eligible for surgery.

Current chemotherapy agents only offer a modest response rate of up to 20% at best, with no significant benefit to the overall survival rate.

New therapies to capitalize on unmet need

Any new therapy for HCC will gain rapid uptake if it shows even a modest increase in efficacy or reduction in toxicity over current regimes. Bayer's Sorafenib has shown potential in early trials to double patient survival time through its novel mechanism of action that cuts off blood supply to the cancer cells.

The demonstrated increase in survival time with Sorafenib is significant in HCC patients as current therapeutic options offer a modest four months survival with considerable toxicity. For HCC patients Sorafenib doubles this survival time to approximately 9 months, and, although this could be described as only a minor improvement for HCC patients, Sorafenib's favorable toxicity profile makes this drug even more appealing, Furthermore the additional time gained for patients to spend with their families and loved ones is invaluable.

Although this is exciting data it needs to be confirmed in larger trials, which are planned. Assuming trials with Sorafenib continue to go well, Datamonitor expects it to hit the US market in 2006.

In the meantime, Eximias Pharmaceutical's Thymitaq and Amgen's T67 are the only agents currently in phase III trials for HCC, however, opinion leaders predict that while these agents provide alternatives to current therapy options they would be unlikely to provide significant improvement in survival for HCC patients. There is optimism that innovative-targeted therapies, which target pathways critical to cancer cell survival, such as Sorafenib, hold promise for HCC patients. Well designed controlled trials of these agents in HCC patients are warranted.

Related research:

• Stakeholder Opinions: Hepatocellular Carcinoma - Growing Market Seeks New Players
• Stakeholder Perspectives: Liver Fibrosis/Cirrhosis - Point of No Return?
• Commercial Insight: Hepatitis B and C - Awaiting New Developments

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