L. Denis et al., EARLY CLINICAL-EXPERIENCE WITH LIAROZOLE (LIAZAL(TM)) IN PATIENTS WITH PROGRESSIVE PROSTATE-CANCER, European journal of cancer, 34(4), 1998, pp. 469-475
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.