Liarozole (R75251) in hormone-resistant prostate cancer patients

Autor: P. Fernandez del Moral, Louis Denis, J. Bruynseels, P. De Porre, G.A. Dijkman, Frans M.J. Debruyne
Rok vydání: 1997
Předmět:
Zdroj: The Prostate. 33:26-31
ISSN: 1097-0045
0270-4137
DOI: 10.1002/(sici)1097-0045(19970915)33:1<26::aid-pros5>3.0.co;2-7
Popis: BACKGROUND Liarozole is an imidazole derivative that has been identified as an inhibitor of the cytochrome P450-dependent all-trans retinoid acid (RA) breakdown. RA is one of the principal endogenous compounds that controls growth and differentiation of epithelial tissues in mammals. METHODS Fifty-five patients with hormone-resistant prostate cancer in progression, following at least first-line androgen ablation therapy, 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 was 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 performance status was 0 (n = 18), 1 (n = 22), 2 (n = 17), and 3 (n = 6). Most patients (80%) used analgesics. RESULTS For 11 out of the 53 patients, treatment lasted less than 1 month (they were therefore not evaluable for response) due to: poor compliance (n = 1); early death (n = 3); side-effects (n = 2); and decline of physical condition and continuous 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 improved. 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 performance status. The prostatic-specific antigen (PSA) response rate was 41%; 15 out of 42 evaluable patients presented a decrease of > or = 50%, whereas PSA normalized in 2 further patients. Most of the side effects mimicked retinoid acid toxicity: cutaneous manifestations (such as dry skin, dry lips, sticky skin, brittle nails, erythema, or itch). All patients experienced one or more of these side effects. Other side effects include nausea, fatigue, and slight alopecia. CONCLUSIONS Liarozole can be an enrichment of the therapeutic armamentarium for treatment of hormone-resistant prostate cancer patients after first-line androgen ablation therapy without serious toxicity.
Databáze: OpenAIRE
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