Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors

Variant liver oestrogen receptor transcripts in hepatocellular carcinoma ar e associated with aggressive clinical course and unresponsiveness to tamoxi fen. To evaluate the impact on survival and on tumour growth of megestrol ( progestin drug acting at post-receptorial level) we enrolled 45 patients wi th HCC characterized by variant liver oestrogen receptors in a prospective, randomized study with megestrol vs. placebo. Presence of Variant oestrogen receptors was determined by RT/PCR. 24 patients were randomized to no trea tment and 21 to therapy with megestrol 160 mg day(-1). Results were analyse d by Kaplan-Meier and Cox methods. Survival of hepatocellular carcinoma cha racterized by variant oestrogen receptors was extremely poor (median surviv al 7 months); megestrol significantly improved survival (18 months) (P = 0. 0090). Tumour growth at one year was significantly slowed down in megestrol -treated patients (P = 0.0212). Bilirubin levels, presence of portal thromb osis, HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival; at multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were factors independe ntly related with survival. (1) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant e strogen receptors and (2) is also able to favourably influence the course o f disease, more than doubling median survival. (C) 2001 Cancer Research Cam paign.