The targeted drug sorafenib (Nexavar) has improved the survival of patients with advanced liver cancer, a fatal disease that is becoming more common worldwide.

The final-stage, randomized study found that patients taking sorafenib lived nearly 3 months longer than patients taking a placebo. This was clinically significant, and the trial was stopped early because preliminary results clearly favored sorafenib.

"For the first time we have a drug that works for these patients," said Dr. Joseph Llovet of the Mount Sinai School of Medicine and the University of Barcelona. He presented the results June 4 at the American Society of Clinical Oncology (ASCO) annual meeting.

Sorafenib is a pill that patients can take at home. The drug, which is approved for kidney cancer, was well tolerated by the 602 patients in the international study. The most common side effects included diarrhea and skin reactions in the hands and feet.

Dr. Llovet noted that there have been more than 100 unsuccessful clinical trials for advanced liver cancer in the last 30 years. Surgery and chemotherapy are used to treat patients in the earlier stages of disease, but there has been no successful "systemic" treatment, such as a drug, for advanced cases.

Sorafenib will now become the standard treatment for patients with advanced liver cancer, and having this regimen as a platform will accelerate clinical trial efforts to identify other agents, said Dr. A. William Blackstock of the Wake Forest University School of Medicine at the meeting.

Until now, experimental therapies for liver cancer have been compared with placebos. Many patients, particularly in the U.S., are reluctant to join clinical trials if they have a 50-percent chance of receiving a sugar pill. Participation in trials may now increase, with sorafenib replacing placebos as the standard control.

"We can now move forward in this disease," said Dr. Blackstock.

The next steps include testing sorafenib earlier in the disease and eventually in combination with other targeted therapies. Bevacizumab (Avastin), erlotinib (Tarceva), and sunitinib (Sutent) have all been tested for liver cancer in phase II studies.

Like these drugs, sorafenib interacts with a small number of proteins. The drug inhibits cell growth and the formation of blood vessels that feed tumors (angiogenesis).

Liver cancer is the fifth most common cancer and the third leading cause of cancer death worldwide. The disease is most prevalent in the developing world, but it appears to be increasing in the U.S. and Europe.

In the trial, the sorafenib group lived on average 10.7 months compared with 7.9 months for the placebo group - a more than 40-percent improvement in survival time.

Sorafenib is the "first convincing and rigorously tested treatment" to show a survival benefit for these patients, said Dr. Philip James Johnson of the Institute for Cancer Studies at Birmingham University in the U.K., who discussed the results in a special session at ASCO.

Dr. Johnson cautioned that it is not yet known how the drug might perform in different ethnic groups and in patients with poor liver function. Most participants were European and had relatively good liver function.

- Edward R. Winstead