Randomized Trial of Leuprorelin and Flutamide in Male Patients With Hepatocellular Carcinoma Treated With Tamoxifen

Abstract

The growth of hepatocellular carcinoma (HCC) is thought to be dependent on androgens, as androgen receptors are present in most of these tumors. The aim of this multicenter trial was to assess the effect of antiandrogens in patients who have advanced HCC. Male patients with advanced HCC were randomized into 2 groups treated with (1) T reatment of patients who have symptomatic or advanced hepatocellular carcinoma (HCC) is still a challenge, because the mean survival is only a few months. 1 As curative treatments such as surgery or percutaneous ablation are excluded, arterial chemoembolization is the preferred palliative option; however, improved survival is only observed in a small percentage of patients with good liver function. 2 No medical treatment has been proven effective. 2 The influence of sex hormones on the growth of HCC has been suspected for a long time. 3 On the basis of experimental studies and findings showing estrogen receptors in tumor cells, treatment with tamoxifen, an antiestrogenic drug effective in breast cancer, 4 has been tested in patients who have unresectable HCC. 5,6 The positive influence of androgens on HCC growth is also supported by other results. First, HCC mainly occurs in males (with a male/female ratio between 5 and 9 1 ), with a poorer outcome in males than in females. 7 Second, occurrence of HCC has been reported in patients treated with androgens 8 or in bodybuilders. 9 Third, serum testosterone has been found to be a predictive factor of HCC occurrence in patients with hepatitis C virus and cirrhosis 10 and in hepatitis B virus carriers. 11 Fourth, androgen receptors have been found in normal livers and in livers with cirrhosis 12 as well as HCC. 13 In tumor cells, androgen receptors seem to be present more frequently and in

The miR-367-3p Increases Sorafenib Chemotherapy Efficacy to Suppress Hepatocellular Carcinoma Metastasis through Altering the Androgen Receptor Signals

“…Nevertheless, clinical trials using various anti-androgens in the attempt to treat HCC have inconsistent conclusions (Groupe d'etude et de traitement du carcinome, H., 2004, Matsuura et al, 1994, Chao et al, 1996). Several hypotheses have been proposed to elucidate this riddle, such as the fact that most of the anti-androgen therapies were developed to reduce/antagonize androgens from binding to AR, but not to target AR itself.…”

“…Previous studies revealed a male predominance in HCC, which suggested that androgen/AR signals may promote hepatocarcinogenesis (Yeh and Chen, 2010). However, the results from several clinical trials using various anti-androgens to treat HCC remain controversial (Groupe d'etude et de traitement du carcinome, H., 2004, Matsuura et al, 1994, Chao et al, 1996). Interestingly, Ma et al revealed that AR might suppress advanced-stage HCC metastasis using liver-specific deletion of AR (L-ARKO) mice model and in vitro HCC cell lines, and over-expressing AR with Sorafenib treatment could better suppress the HCC progression at late stages (Ma et al, 2012).…”

Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis

“…Results from several studies on the use of anti-androgens to manage HCC remain controversial (Di Maio, et al 2008; Hépatocellulaire. 2004).…”

Interplay of estrogen receptors and FOXA factors in the liver cancer

“…Estrogens, including estradiol and diethylstilbestrol, have occasionally been employed to treat cancers, including HCC; however, both preventing and promoting cancer effect were recorded (Di Maio et al, 2006; Kalra et al, 2008; Lawrence et al, 2007). Androgens, including testosterone and dihydrotestosterone, have been shown to promote HCC; however, clinical research employing anti-androgens for HCC treatment had many disappointing consequences, with few beneficial effects or even worse survival for patients (Di Maio et al, 2008; Groupe d’Etude et de Traitement du Carcinome, 2004). Finally, a recent study reported dual yet opposing roles of hepatic AR: promoting HCC initialization and suppressing HCC metastasis (Ma et al, 2012).…”