Systemic treatment of hepatocellular carcinoma.

The results of systemic treatments for hepatocellular carcinoma are currently disappointing. In patients with advanced disease, none of the tested treatments (particularly systemic chemotherapy or hormonal treatment, such as tamoxifen) demonstrated an unequivocal benefit in terms of survival, and the trials including the largest numbers of patients have constantly been negative. After successful treatment of a first tumour, the most promising adjuvant strategy seems to be the use of interferon to treat patients who have hepatitis C infection. Nevertheless, only a few small randomized controlled trials have been performed and this result should be confirmed. Methodological improvement of clinical trials is needed, as major bias has often hampered the interpretation of the results. As recommended at a recent international conference in Barcelona, the most reliable methods for assessing the clinical outcome of a treatment in hepatocellular carcinoma are large randomized trials that each include a control arm of untreated patients, with overall survival as the primary endpoint, and an intention-to-treat analysis. New therapeutic strategies should be developed. Drugs such as vitamin D or vitamin A derivatives and inhibitors of COX-2 or angiogenesis could have a favourable influence on tumour growth. Some of these drugs are currently being tested in preliminary studies or even large randomized trials.