Use of tamoxifen in hepatocellular carcinoma: A review and paradigm shift

Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which there are no uniformly efficacious treatment available presently. Th e oral anti-oestrogen drug, tamoxifen, has been used in such patients, base d on the belief that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen via a receptor-mediated process. In this review, we ex amine the trials reported in the literature using tamoxifen in hepatocellul ar carcinoma. Randomized controlled trials with tamoxifen have so far revea led mixed results. We propose that this may be due to the fact that the mec hanism of action of tamoxifen in hepatocellular carcinoma is via an oestrog en-receptor independent pathway that requires much higher doses of tamoxife n for activation than those used in the trials so far. Thus there must be a paradigm shift to dissociate the action of tamoxifen from oestrogen recept ors in hepatocellular carcinoma. This means that future trials with tamoxif en in hepatocellular carcinoma should use higher doses of tamoxifen, at lea st four to eight-fold that of the dose that is efficacious in an oestrogen- receptor dependent mechanism. (C) 2000 Blackwell Science Asia Pty Ltd.