LIAROZOLE (R75251) IN HORMONE-RESISTANT PROSTATE-CANCER PATIENTS

BACKGROUND. Liarozole is an imidazole derivative that has been identif ied as an inhibitor of the cytochrome P450-dependent all-trans retinoi d acid (RA) breakdown. RA is one of the principal endogenous compounds that controls growth and differentiation of epithelial tissues in mam mals. METHODS. Fifty-five patients with hormone-resistant prostate can cer in progression, following at least first-line androgen ablation th erapy, were evaluated. Thirty-one patients were treated with Liarozole 300 mg b.i.d., while 24 patients started with 150 mg b.i.d., which wa s increased to 300 mg b.i.d. after 4 or 8 weeks. Two patients were not evaluable because they withdrew after initial consent. The WHO perfor mance status was 0 (n = 18), 1 (n = 22), 2 (n = 17), and 3 (n = 6). Mo st patients (80%) used analgesics. RESULTS. For 11 out of the 53 patie nts, treatment lasted less than 1 month (they were therefore not evalu able for response) due to: poor compliance (n = 1); early death (n = 3 ); side-effects (n = 2); and decline of physical condition and continu ous progression (n = 4). One patient refused to report for follow-up. In all responders, except one, the dose was increased to 300 mg b.i.d. In 23 of the 42 patients evaluable for response, the pain score impro ved. In 5 patients the pain score had reduced from 2 or 3 to 0. In 11 out of the 42 patients there was a 1-point improvement of WHO performa nce status. The prostatic-specific antigen (PSA) response rate was 41% ; 15 out of 42 evaluable patients presented a decrease of greater than or equal to 50%, whereas PSA normalized in 2 further patients. Most o f the side effects mimicked retinoid acid toxicity: cutaneous manifest ations (such as dry skin, dry lips, sticky skin, brittle nails, erythe ma, or itch). ALI patients experienced one or more of these side effec ts. Other side effects include nausea, fatigue, and slight alopecia. C ONCLUSIONS. Liarozole can be an enrichment of the therapeutic armament arium for treatment of hormone-resistant prostate cancer patients afte r first-line androgen ablation therapy without serious toxicity. (C) 1 997 Wiley-Liss, Inc.