Tamoxifen for adults with hepatocellular carcinoma

Rationale Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Tamoxifen has been evaluated in randomised clinical trials in people with hepatocellular cancer. The reported results have been inconsistent. Objectives To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment. Search methods We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024. Eligibility criteria Parallel‐group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross‐over trials, we would have included only the first trial phase. We did not consider data from quasi‐randomised trials for analysis. Outcomes Our critical outcomes were all‐cause mortality, serious adverse events, and health‐related quality of life. Our important outcomes were disease progression, and adverse events considered non‐serious. Risk of bias We assessed risk of bias using the RoB 2 tool. Synthesis methods We used standard Cochrane methods and Review Manager. We meta‐analysed the outcome data at the longest follow‐up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random‐effects model. We summarised the certainty of evidence using GRADE. Included studies We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single‐centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia‐Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co‐interventions were best support