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Therapeutic Options in Hepatocellular Carcinoma

  • Review Article
  • Published:
American Journal of Cancer

Abstract

Hepatocellular carcinoma (HCC) is common in Africa as well as south eastern Asia, and is usually related to chronic hepatitis B virus infection although chronic hepatitis C virus infection and alcohol abuse also play a major role. Mass vaccination against the hepatitis B virus in neonates has been undertaken in Taiwan and South Africa with encouraging results.

The treatment of choice for HCC is surgery, but radical resection is only feasible in a small percentage of patients because of the advanced nature of the disease and underlying liver cirrhosis. If surgical resection is not feasible, intra-arterial chemoembolization may reduce the size of tumors providing good palliation, and possibly render inoperable tumors operable. Locally ablative therapies including percutaneous ethanol injection, cryosurgery, microwave coagulation, and radiofrequency thermal ablation are useful in patients with limited disease, but are methods that are only feasible in highly specialized units. Liver transplantation, which is also only available in highly specialized centers, has unfortunately been disappointing. Unresectable HCC has a very poor prognosis, as the disease is highly refractory to most chemotherapy agents, possibly as a result of overexpression of the multidrug resistance gene, mdr1. Overall response rates of 10–15% have been reported with most chemotherapeutic agents, with doxorubicin probably being the most active agent. Other agents studied include fluorouracil as well as the newer oral fluoropyrimidines, etoposide, gemcitabine, anthracycline analogues including mitoxantrone, epirubicin, and pegylated liposomal doxorubicin, as well as cisplatin and the direct thymidylate synthase inhibitors raltitrexed and nolatrexed. Other agents including tamoxifen, tyrosine kinase inhibitors, thalidomide, interferons, and clofazimine have also been studied. Administration of viral vectors containing the p53 gene, or other tumor suppressor and suicide genes, is also a possible future therapy.

Unfortunately as current approaches still remain unsatisfactory, especially in patients with advanced unresectable disease, newly diagnosed patients should, whenever available, be entered onto clinical studies with new agents which may result in better therapies for this highly refractory disease.

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  1. Division of Medical Oncology, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, Parktown, 2193, South Africa

    Paul Ruff

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Ruff, P. Therapeutic Options in Hepatocellular Carcinoma. Am J Cancer 3, 119–131 (2004). https://doi.org/10.2165/00024669-200403020-00004

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