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.