CGS 16949A is a very potent and highly selective inhibitor of the
aromatase enzyme system in vitro and of
estrogen biosynthesis in vivo. These characteristics are reflected in the marked efficacy with which it affects growth of
estrogen-dependent 7,12-dimethylbenz(a)antracene-induced mammary
carcinomas in intact female Sprague-Dawley rats. Daily p.o. treatment of
tumor-bearing rats for 42 days with
CGS 16949A at doses of 1.0 to 8.0 mg/kg caused almost complete regression of palpable
tumors and almost totally suppressed the appearance of new
tumors. A dose of about 0.1 mg/kg corresponded to the 50% effective dose, and a fully effective dose was estimated to be about 2.0 mg/kg. Eight to 10 days after
cessation of treatment,
tumor regrowth was observed. No unexpected side-effects were noted during the course of treatment.
Tumors, which were allowed to regrow after a first treatment with
CGS 16949A, were similarly efficaciously suppressed with a second treatment with
CGS 16949A. Continuous long-term treatment with 2.0 mg/kg for 27 wk caused complete regression of
tumors, suppressed the appearance of new
tumors completely, and significantly prolonged the survival time of the
tumor-bearing rats. This treatment schedule caused no major hematological or blood chemistry changes and was very well tolerated.
CGS 16949A was ineffective against transplantable
hormone-independent
tumors such as R-3230AC mammary
carcinoma, 11095 prostate
carcinoma,
leukemia L1210, and
B16 melanoma.