166                                                                                                                             Hepatocellular Carcinoma

30.                Hepatocellular Carcinoma

30.1          General considerations

Curative therapy options, such as hepatic resection or liver transplantation, remain limited to a minority of patients. Percutaneous locoregional and intra-arterial treatments (incl. chemoembolization) therefore have gained interest, because they are less invasisve than surgery , and result in comparable gains in survival. They are feasible only in patients with disease confined to the liver, however. For patients with extrahepatic disease or a blocked portal vein system , systemic chemotherapy-although having been effective in not more than 20 % of patients for many years is the only treatment option available .

Because of the still limited scope of success of therapy, prevention also would be of great importance. There is strong evidence to suggest that infection with hepatitis B virus and cirrhosis associated with hepatitis C virus play a role in the development of hepatocelluar carcinoma, and for patients with hepatitis C virus cirrhosis it could be shown that interferon significantly reduces that risk.

Literature: for review e.g.

            AGUAYO and PATT, Semin. Oncol. 28 (2001): 502-513 (non-surgical 

            treatment options)

            BERGSLAND and VENOOK, Curr, Opin. Oncol. 12 (2000): 357-361

            HUSSAIN et al Ann Oncol. 12 (2001): 161- 172

            LEUNG and JOHNSON, Semin. Oncol. 28 (2001): 514-520

            NAKAKURA and CHOTI, Oncology 14 (2000): 1085-1102

            SCHAFER and SORRELL, Lancet 353 (1999): 1253-1257

            SIMONETTI et al, Ann. Oncol. 8(1997): 2403-2413

            TREVISANI et al, J. Clin. Gastroenterol. 32 (2001): 383-389

            (chemoembolization)

30.2        Systemic intravenous therapy

30.2.1 Single agent chemotherapy

Any benefit of chemotherapy is most likely in patients with a good performance status and a satisfactory  liver function.

The most commonly used single agents are doxorubicin, epirubicin and mitoxantrone. Other agents include 5-fluorouracil, etoposide, cisplatin and ifosfamide.

Literature: e.g.

            COLLEONI et al, Oncology 49 (1992): 139-142 (mitoxantrone)

            DUNK et al, J. Hepatol. 1 (1985): 395-404 (mitoxantrone)

            FALKSON et al, Cancer 60 (1987): 2141-2145 (cisplatin)

            LAI et al, Cancer 62 (1988): 479-483

            LIN et al, Cancer Chemother, Pharmacol. 31 (1993): 338-339

            MELIA et al, Cancer 51 (1983): 206-210 (etoposide)

            POHL et al, Chemotherapy 47 (2001) : 359-365 (epirubicin)

30.2.2 Combination chemotherapy

Combination chemotherapy can not generally be recommended as standard therapy outside of clinical trials. Therefore only one representative expample of a regimen is given which resulted in complete pathologic remissions and conversation to resectable disease.

Hepatocelluar Carcinoma                                                                                                                             167

            PIAF  

            To be repeated every 3 – 4 weeks

            Literature:

                        LEUNG et al, Clin. Cancer Res . 5 (1999): 1676-1681

30.2.3   Interferon alpha        

The use of (high-dose) interferon alpha as a single agent declined over the years, but it still has its role in combination with cytotoxic drugs (see 29.2.2 PIAF), as well as for prevention of the development of hepatocellular carcinoma in patients with hepatitis C cirrhosis.

Literature:

LAI et al, Hepatology 17 (1993): 389-394 (randomized trial of high-dose interferon vs control)

                        PAPATHEODORIDIS et al, Aliment. Pharmacol. Ther.15 (2001): 689 –  

                        698 (meta-analysis of the effect of interferon therapy on the development 

                        of hepatocellular carcinoma in patients with hepatitis C virus-related      

                        cirrhosis)

                        THEVENOT et al, J, Viral. Hepat. 8 (2001): 48-62 (meta-analysis of 

                        interferon randomized trials in the treatment of viral hepatitis C)

30.2.4 Somatostatin analogs

A randomized trial of octreotide vs no treatment has shown a significant survival benefit in the treated patients. Larger scale clinical trials are required, however, to confirm this promising result.

Literature:

            KOUROUMALIS, Chemotherapy 47 (Suppl 2) (2001): 150-161

30.2.5 Tamoxifen

Randomized trials with tamoxifen have so far revealed contradictory results, which presently do not support its routine use.

Literature: for review e.g.

            TAN et al, J. Gastroenterol. Hepatol. 15 (2000): 725 – 729

30.3        Hepatic intra-arterial therapy (HIA)

5-Fluorouracil and floxuridine are the agents most commonly used for HIA, others are doxorubicin, mitoxantrone, epirubicin and cisplatin.

Literature: for review e.g.

            AGUAYO and PATT, Semin. Oncol. 28 (2001): 503-513

30.4        Chemoembolization

Various agents have been tested for hepatic arterial embolization, including gel foam, starch microspheres, collagen, lipiodol.

Literature: for review e.g.

            AGUAYO and PATT, Semin. Oncol. 28 (2001): 503-513

            TREVISANI et al, J. Clin. Gastroenterol, 32 (2001): 383-389