TREATMENT OF HEPATOCELLULAR-CARCINOMA WITH COMBINED SUPPRESSION AND INHIBITION OF SEX-HORMONES - A RANDOMIZED, CONTROLLED TRIAL

We tested the hypothesis that a combination of sex hormone suppression and inhibition of their target receptors might improve survival for p atients with hepatocellular carcinoma (HCC). Eighty-five consequent, p reviously untreated HCC patients with inoperable disease, were randomi zed to receive the luteinizing hormone-releasing hormone (LR-RH)-analo gue triptorelin and the antiestrogen tamoxifen (33 patients) or tripto relin plus the antiandrogen flutamide (23 patients), or only placebo ( 29 patients) in a double blind fashion. All groups were comparable as to age, sex, tumor extension, underlying cirrhosis and biochemical par ameters. The tamoxifen (TMX) group had a significantly longer survival (282 days) compared with flutamide (112 days) and with placebo (127 d ays) groups (P = .0238, log rank test). The upper quartile of patients in the TMX group lived 384 days or longer, and most of them (57.1%) w ere women (P < .0005), in contrast to the upper quartile of the placeb o (170 days, 16.7% women) and the flutamide group (134 days, 33.3% wom en). The calculated tumor volume doubling time (TVDT) was significantl y higher in the TMX group (296 days) than in the other two groups (99 and 101 days for placebo and flutamide groups, respectively, P = .023) . In a Cox proportional hazards model, the TMX treatment, along with t he baseline Okuda's HCC stage, the hepatitis B surface antigen, the po rtal vein diameter, the carcino embryonic antigen (CEA) and a self-ass essment score of quality of life, were covariates predicting survival. Although the degree of serum sex hormone suppression was not a signif icant predictor of survival, the interaction of female sex and TMX tre atment, it was (P = .0052), We conclude that TMX treatment significant ly prolongs survival and the TVDT in unresectable HCC. The effect is m ost pronounced in female patients and is unrelated to sex hormone supp ression.