Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, prostate cancer, metastasis, retinoic acid metabolism, differentiation therapy, liarozole, HIGH-DOSE KETOCONAZOLE, ADENOCARCINOMA, THERAPY, Aged, Aged, 80 and over, Alkaline Phosphatase, Androgen Antagonists, Antineoplastic Agents, Hormonal, Hormones, Humans, Imidazoles, Male, Middle Aged, Pain, Pain Measurement, Pilot Projects, Prostate-Specific Antigen, Prostatic Neoplasms, Survival Analysis, Treatment Outcome, 1112 Oncology and Carcinogenesis, 1117 Public Health and Health Services, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

Liarozole (Liazal) is the first retinoic acid (RA) metabolism blocking agent (RAMBA) in clinical practice. RAMBA therapy promotes differentiation and inhibits proliferation by increasing endogenous RA in tumours. Liarozole was investigated in two open-label pilot studies of 100 patients with progressive prostate cancer in relapse despite previous androgen ablation. Liarozole (150-300 mg twice daily, for > or = 1 month) produced > or = 50% reduction in prostate specific antigen (PSA) serum levels in 15 of 30 evaluable patients in study 1 (50%) and 10 of 55 patients in study 2 (18%). PSA 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 androgens did not alter during chronic treatment with liarozole nor at adrenocorticotrophic hormone (ACTH) stimulation test. Liarozole did not alter plasma levels of adrenal androgens or cortisol. Cortisol response 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 treatment option in prostate cancer.