Treatment of advanced hepatocellular carcinoma with tamoxifen and the correlation with expression of hormone receptors: a prospective randomized study. Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial. Controlled trial of tamoxifen in patients with advanced hepatocellular carcinoma. Treatment of hepatocellular carcinoma with tamoxifen: a double-blind placebo-controlled trial in 120 patients. Controlled clinical trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma. Randomized controlled trial of tamoxifen versus placebo in inoperable hepatocellular carcinoma. High-dose tamoxifen in the treatment of inoperable hepatocellular carcinoma: A multicenter randomized controlled trial. Tamoxifen does not improve survival of patients with advanced hepatocellular carcinoma.
A prospective randomized study was performed to test the hypothesis that tamoxifen might improve the survival of patients with advanced hepatocellular carcinoma (HCC) and to correlate the response of treatment with the expression of hormone receptors.
                One hundred nineteen patients with advanced and otherwise untreatable HCC were included in a placebo-controlled, single-blind trial. The patients were randomized to tamoxifen group (61 patients) and control group (58 patients) and were prescribed with a daily dose of 30 mg of tamoxifen and placebo, respectively. Immunohistochemical tests for estrogen and progesterone receptors were performed on the tumor tissues obtained from 66 patients. All patients were closely monitored and the survival outcome of the two groups of patients was compared and stratified according to the hormonal receptor status.
                There was no difference in the 1-month mortality rates (32.8% vs. 43.1%, p = 0.246) and the median survival (44 days vs. 41 days, p = 0.703) between the tamoxifen group and the control group. Furthermore, the expression of hormone receptors in the tumors did not affect the survival outcome of the patients treated with tamoxifen. None of the patients who survived longer than 3 months had tumor that had partial response to tamoxifen treatment on follow-up imaging study.
                Tamoxifen has no efficacy in the treatment of patients with advanced HCC and response to treatment was not affected by the expression of hormone receptors. In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment.
                The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death.
                496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis.
                the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis. Thirty-six consecutive patients with advanced hepatocellular carcinoma and chronic liver disease were randomly allocated to two groups: group I included 20 patients who were treated with 10 mg bid. tamoxifen and group II with 16 non-treated patients. The two groups were homogeneous according to clinical and analytical data. Survival curves in the tamoxifen-treated patients improved significantly when compared with the non-treated group (p = 0.01). Cumulative survival at the end of the first year was 48.5% in the treated patients and 9.1% in controls. Median survival was 261 days in the treated group vs. 172 in the non-treated group (p < 0.05). Complications of cirrhosis and worsening of the performance status test occurred less in the treated patients than in the controls, but not significantly so. Tamoxifen was well tolerated and no marked side effects were observed. In this series, tamoxifen improved survival in patients with advanced hepatocellular carcinoma. The progression of hepatocellular carcinoma may be influenced by estrogens. This has offered the rationale for evaluating the therapeutic usefulness of estrogen-receptor blockers; it is being debated whether long-term tamoxifen administration improves survival in patients with this neoplasm. The aim of this study was to assess the efficacy of tamoxifen administration in the treatment of hepatocellular carcinoma.
                One hundred twenty patients with this neoplasm who were not suitable for surgery, ethanol injection, or transarterial embolization were included in a placebo-controlled trial and randomized to tamoxifen, 20 mg/day per os, (group A, n = 58) or placebo (group B, n = 62). Patients with terminal diseases were excluded.
                Both groups were similar with regard to sex, age, liver function (Child-Pugh's score, 6.5 +/- 1.4 vs. 6.4 +/- 1.4), baseline performance status, and tumor stage. Tamoxifen had no antitumoral effect with no differences in the survival between groups (1- and 2-year actuarial rate: group A, 51% and 27%; and group B, 43% and 29%; P = 0.75), even when stratifying patients according to baseline status. Furthermore, there were no differences in the probability of disease progression (P = 0.46) and baseline performance status maintenance (P = 0.93) during follow-up.
                Tamoxifen has no efficacy in the treatment of patients with advanced hepatocellular carcinoma. Following reports that specific estrogen receptors could be detected in samples of hepatocellular carcinoma tissue, a prospective randomized controlled trial was undertaken in 59 patients, half of whom received doxorubicin (60 mg/m2 at 3-week intervals) and half doxorubicin and tamoxifen (10 mg twice per day). Response occurred in three (11%) of those patients receiving doxorubicin alone and in four (16%) of those given both drugs. This difference was not statistically significant nor was the difference in survival when compared by life-table analysis. One patient treated with both drugs achieved complete remission for 30 months which was maintained (on tamoxifen alone) for 18 months before death from a non-tumor-related condition. Tamoxifen may have a role in maintenance of doxorubicin-induced remissions. A randomized controlled trial of tamoxifen (60 mg/die) versus placebo was performed in patients with cirrhosis and advanced inoperable hepatocellular carcinoma. Twenty-two patients were matched and coupled for sex, age, Child-Pugh class and tumour mass and then randomized to tamoxifen or placebo. Median survival was 74 weeks in the tamoxifen group (range 27 to 144 weeks) and 52 weeks in the placebo group (range 4 to 112 weeks). The survival of patients treated with tamoxifen improved significantly compared to the controls (Logrank-test, p = 0.04). These findings suggest that the effect of the antiestrogen tamoxifen is both statistically and clinically significant in increasing survival in patients with advanced hepatocellular carcinoma. In the Asia-Pacific region and elsewhere, almost 85% of patients with hepatocellular carcinoma (HCC) are inoperable at diagnosis and have a dismal prognosis. Tamoxifen (TMX) is believed to inhibit HCC positive for estrogen receptor (ER), but most HCCs are ER negative. Results of previous phase 3 trials in inoperable HCC have been conflicting and inconclusive. At higher doses, however, TMX inhibits HCC through ER-independent mechanisms. A multicenter randomized controlled trial was performed to assess the role of high-dose TMX versus placebo (P) in the treatment of patients with inoperable HCC with respect to survival and quality of life (QoL). A total of 329 patients from 10 centers in 9 countries in the Asia-Pacific region enrolled in a double-blind randomized controlled trial of TMX 120 mg/d (TMX120) against P as a control arm with an intermediate dosage of TMX 60 mg/d (TMX60) to assess possible dose response. An independent data monitoring committee reviewed all aspects of the trial. QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. Three-month survival rates for the P, TMX60, and TMX120 groups were 44%, 41%, and 35%, respectively, with a statistically significant trend difference in survival across the 3 treatment regimens (P =.011). There was a significantly higher risk of death in the TMX120 group compared with the P group (hazard ratio, 1.39; 95% confidence interval, 1.07-1.81). Adverse drug reactions were reported in 3% (9 patients), and 8 patients were lost to follow-up. In conclusion, TMX does not prolong survival in patients with inoperable HCC and has an increasingly negative impact with increasing dose. No appreciable advantage to QoL with TMX was observed. To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.