Liarozole.
Liarozole prevents the catabolism of retinoic acid via inhibition of 4-hydroxylase and exhibits retinoid-sparing and retinoid-mimetic effects in vivo. Liarozole is also a potent inhibitor of estrogen (via inhibition of aromatase) and testicular androgen synthesis (inhibition of 17, 20-lyase). Although testosterone levels decrease in vivo after single dose administration of liarozole, testosterone levels normalise as a result of pituitary feedback after multiple doses. Liarozole reduced the tumour size of androgen-dependent and -independent prostatic carcinomas in animal models. Liarozole also demonstrated chemopreventive activity in vivo. In phase I and II trials in patients with relapsed prostate cancer, liarozole achieved a complete response (assessed using prostate specific antigen levels) in 4% and a partial response in 26% of patients. Cutaneous adverse events, similar to those associated with excess levels of retinoic acid, were the most frequently reported events associated with liarozole.
Bryson
H M
HM
Adis International Limited, Auckland, New Zealand.
Wagstaff
A J
AJ
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D018931:Antineoplastic Agents, Hormonal; D007093:Imidazoles; C061121:liarozole