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Hepatocellular Carcinoma Treatment Options Remain Limited, but New Avenues Are Being Explored: Presented at HEP DART

By Bonnie Darves

KOHALA COAST, HI -- December 20, 2005 -- Until better therapies are discovered for hepatocellular carcinoma (HCC), the management approach should focus on intervention through chemoprevention, better screening and earlier diagnosis, researchers stated here at the Frontiers in Drug Development for Viral Hepatitis HEP DART 2005 meeting.

Despite advances in radiation therapy and the recent proliferation of effective anti-cancer drugs, those developments have had little effect on prognosis for patients with HCC, for which liver transplant remains the only potentially curative treatment, presenters acknowledged here during a presentation on December 13^th.

Hepatocellular carcinoma often occurs in advanced hepatitis C (HCV) and now afflicts an estimated 1 million individuals worldwide.

"One of the primary reasons so many hepatocarcinoma patients are untreatable is that by the time they are diagnosed, the disease is too far advanced for the tumor to be resectable," said Eddie Cheung, MD, Clinical Professor of Internal Medicine and Gastroenterology/Hepatology, University of California-Davis, Sacramento, California, United States. "That's why 6-month survival rates are so grim."

Studies have shown that resection is only possible when tumors are no larger than 5 cm in diameter and when there are no more than three nodules. An estimated 5% of HCC patients are candidates for resection, and even with resection, 3-year recurrence rates are between 45% and 60%. In addition, most trials of chemotherapy regimens have produced such poor results that those therapies have focused primarily to palliation.

On the chemotherapy front, however, preliminary data from a phase 3 trial comparing a novel thymidylate synthase inhibitor, Thymitaq, with adriamycin, suggests that Thymitaq may eventually emerge as a therapeutic option for unresectable HCC. "Thymitaq looks better than adriamycin at this point," Cheung said.

Even with such distressing statistics and the paucity of effective treatments besides transplantation, a few emerging avenues appear to offer some promise, Dr. Cheung noted. He cited recent trials of high-dose percutaneous ethanol injection (PEI) -- which, in essence, involves "smashing the tumor," he said -- radiofrequency ablation (RFA) and transarterial chemoembolization.

In a 2004 trial of 157 patients comparing standard and high dose PEI and RFA, 92% of patients who received high-dose PEI and 96% of RFA patients experienced complete tumor necrosis. Three-year progression rates were 26.4% for high-dose PEI and 15.3% for RFA, and 3-year survival rates were 60.3% and 71.1%, respectively.

Transarterial chemoembolization, in a metanalysis of seven trials, had a 2-year survival rate of 41% but was associated with a high risk of infection, Dr. Cheung noted.

In a recent trial combining standard radiotherapy, to which HCC responds, with external-beam radiation, the approach stabilized tumor progression in 58% of the 36 participants.


[Presentation title: Therapy for Hepatocellular Carcinoma: Current Therapies and Needs. Abstract 41]

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