Tamoxifen is not effective in good prognosis patients with hepatocellular carcinoma

Large randomised clinical trials and systematic reviews substantiate that tamoxifen is ineffective in improving survival of patients with hepatocellular carcinoma (HCC). However, a recent report suggested that the drug might prolong survival among patients with well preserved liver function. The aim of this paper is to validate this hypothesis.

We used the updated database of the phase 3 randomised CLIP-1 trial that compared tamoxifen with supportive therapy. Primary endpoint was overall survival. Treatment arms were compared within strata defined according to the Okuda stage and the CLIP-score. Survival differences were tested by the Log-rank test.

Tamoxifen was not effective in prolonging survival in Okuda I-II subgroup (p = 0.501). Median survival times were equal to 16.8 (95%CI 12.7-18.5) months for tamoxifen and 16.8 (95%CI 13.5-22.4) months for the control arms; 1-year survival probabilities were equal to 58.8% (95%CI 51.7-65.8) and 59.4 (95%CI 52.5-66.2), respectively. Similar results were observed in the better CLIP subgroup (score 0/1), without evidence of difference between the two treatment arms (p = 0.734). Median survival times were equal to 29.2 (95%CI 20.1-36.4) months with tamoxifen and 29.0 (95%CI 23.3-35.2) months without; 1-year survival probabilities were equal to 80.9% (95%CI 72.5-89.3) with tamoxifen and 77.1% (95%CI 68.6-85.7) for the control arm.

The recent suggestion that tamoxifen might be effective in the subgroup of patients with better prognosis is not supported by a reanalysis of the CLIP-1 trial. Tamoxifen should no longer be considered for the treatment of HCC patients and future trials of medical treatment should concentrate on different drugs.