EARLY CLINICAL-EXPERIENCE WITH LIAROZOLE (LIAZAL(TM)) IN PATIENTS WITH PROGRESSIVE PROSTATE-CANCER

Liarozole (Liazal (TM)) is the first retinoic acid (RA) metabolism blo cking agent (RAMBA) in clinical practice. RAMBA therapy promotes diffe rentiation and inhibits proliferation by increasing endogenous RA in t umours. Liarozole was investigated in two open-label pilot studies of 100 patients with progressive prostate cancer in relapse despite previ ous androgen ablation. Liarozole (150-300mg twice daily, for greater t han or equal to 1 month) produced greater than or equal to 50% reducti on in prostate specific antigen (PSA) serum levels in 15 of 30 evaluab le patients in study 1 (50%) and 10 of 55 patients in study 2 (18%). P SA responders had more marked reductions in prostatic acid phosphatase , alkaline phosphatase and symptom scores for bone pain and urological symptoms, and improved general well being. Plasma levels of adrenal a ndrogens did not alter during chronic treatment with Liarozole nor at adrenocorticotrophic hormone (ACTH) stimulation test. Liarozole did no t alter plasma levels of adrenal androgens or cortisol. Cortisol respo nse to ACTH stimulation was slightly blunted. Liarozole was generally well tolerated. Dermatological adverse events were probably related to increased intracellular RA. Liarozole appears to be a promising treat ment option in prostate cancer. (C) 1998 Elsevier Science Ltd. All rig hts reserved.