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Drug therapy of liver cancer

There is no documented benefit by the use of adjuvant chemotherapy in HCC.

Hepatocellular carcinoma (HCC) has been considered a chemo-resistant cancer type. Still, weekly treatment with Adriamycin in patients with an inoperable cancer who are in good general health has been commonly applied. In a recent randomized phase III study, Adriamycin increased survival time compared to an interactive experimental medication (3).

Sorafenib is a new multi-kinase inhibitor which interacts with both cell proliferation and angiogenesis. A large randomized phase III study has shown that sorafenib increases survival time from 7.9 to 10.7 months compared to placebo (4).

Sorafenib was given only to Child-Pugh A patients, causing diarrhea and hand-foot syndrome as the most important side effects. In a recent randomized phase II study, a combination of sorafenib and Adriamycin showed a survival time of 13.7 months versus only 6.5 months median survival for Adriamycin alone (5).

Based on available literature, it is believed to be reasonable that HCC patients with Child-Pugh A status should initially be assessed for palliative treatment with sorafenib.

Inoperable HCC/metastatic illness

Many patients have a metastatic or inoperable illness at the time of diagnosis. Patients without significant liver failure can be given palliative oncology treatment.

Chemoembolization

Chemoembolization (TACE) is a combination of embolization of a hepatic artery branch supplying the tumor and chemotherapy administered in a hepatic artery. The method exploits the fact that in normal liver tissue, the arteries supply only 20–25% of the circulation versus 85–100% in HCC. Chemoembolization of locally advanced HCC is controversial partly due to lack of an international standard procedure. The two randomized studies available (80 and 112 patients) have shown an increase of survival for chemoembolization at 3 years from 3% to 26% and at 2 years from 27% to 63% (6,7).

In a meta-analysis of randomized and non-randomized studies, it was concluded that TACE improves long-term survival (3 year survival increased by 28%) and reduces the frequency of recurrence (28%).

Substances used are doxorubicin, mitomycin C, and cisplatin. Internationally, it is assumed that about 10% of patients with HCC will be suitable for chemoembolization.  

The following criteria for TACE treatment apply:

  • The patient is inoperable.
  • No tumor trombi in the portal system.
  • The main stem of the portal vein must be open. 
  • Tumor < 10 cm (cases with a diameter greater than this are assessed individually)
  • Multifocal tumors with diffuse liver involvement: relative contraindication
  • Child A-B, not Child C

At Oslo University Hospital, a protocol for TACE, with drug eluting beads loaded with doxorubicin is used. The advantage of this technique is the higher local concentration of doxorubicin and less systemic side effects.

TACE as pre-treatment to a resection or transplantation may be considered.

TACE can also be combined with RFA.

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