title: Antitumoral effects of liarozole in androgen-dependent and independent R3327-Dunning prostate adenocarcinomas.
abstract: We examined the in vivo antitumoral effects of liarozole against androgen-dependent and independent Dunning rat prostatic tumors. Liarozole, applied as a dietary admixture, at a dose of 120 mg./100 gm. food, equivalent to 100 mg./kg. per day, inhibited the growth of the slow growing, well-differentiated, androgen-dependent Dunning-H tumor (median tumor volume decrease of 60%). At the same dose it also significantly reduced the growth of the androgen-independent, moderately differentiated PIF-1 (-60%) and androgen-independent, anaplastic AT-6 tumors (-73%). The growth of AT-6 sq tumor showing squamous metaplasia was unaffected by liarozole. When administered by oral gavage, liarozole at 40 (-82%) mg./kg. twice a day was as effective as castration (-92%) in reducing the androgen-dependent, poorly differentiated Dunning R3327-G tumor. Liarozole, administered by gavage, twice a day, also significantly reduced median tumor volume in the androgen-independent, AT-6 sq (-90% at 60 mg./kg., twice a day). This difference between liarozole administration by gavage and food admixture will have to be taken into account in further experimental studies. Inhibition of the growth of several androgen-dependent and, chiefly, androgen-independent Dunning prostate carcinoma sublines that differ widely in their histological degree of differentiation and growth rate suggests that liarozole may be a suitable agent for evaluation in second line treatment of hormone refractory prostate carcinoma in patients who relapse after androgen ablation.
authors.affiliation: Department of Urology, University Hospital Nijmegen, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: Dijkman
authors.forename: R J
authors.initials: RJ
authors.lastname: Van Moorselaar
authors.forename: R
authors.initials: R
authors.lastname: Van Ginckel
authors.forename: P
authors.initials: P
authors.lastname: Van Stratum
authors.forename: L
authors.initials: L
authors.lastname: Wouters
authors.forename: F M
authors.initials: FM
authors.lastname: Debruyne
authors.forename: J A
authors.initials: JA
authors.lastname: Schalken
authors.forename: R
authors.initials: R
authors.lastname: de Coster
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000728:Androgens; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D007093:Imidazoles; C061121:liarozole