Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: Results of a European organization for research and treatment of cancer multicentric double-blind trial

Purpose: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). Patients and Methods: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. Results: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. taking the factorial design into account, comparison of survival showed no significant difference between Anandron containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. Conclusion: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC. (C) 1998 by American Society of Clinical Oncology.