Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase.

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.