Pregnancy-dependent TPDMT-4 mammary
tumors, characterized by requiring
estrogen,
progesterone, and
pituitary hormones for growth, grew continuously in female
DDD mice carrying pituitary isografts. The experimental model was used to investigate the antitumor effects of two p.o.
steroids,
mepitiostane and
fluoxymesterone. When
tumors implanted with pituitary isografts into the fat-pad reached palpable size, animals received 6 doses/week of 0.1, 0.3, 1.0, and 3.0 mg of either
steroid intragastrically.
Mepitiostane significantly suppressed
tumor growth with regression in 25 and 29 percent of animals at 1.0 and 3.0 mg, respectively, but had no inhibitory effects at other doses.
Fluoxymesterone retarted
tumor growth during the first week of treatment at 3.0 mg but finally had no inhibitory effects at any doses. Under similar conditions
ovariectomy caused
tumor regression immediately, and
epitiostanol, the parent
steroid of
mepitiostane, significantly suppressed
tumor growth when given in 3
injections/week of 0.5 mg s.c. Tumous had papillary structures and almost lacked secretory activity. A comparison of these findings to those obtained with earlier generations suggests that TPDMT-4
tumors became less sensitive to the antitumor effect of
epitiostanol and were able to grow at lower
hormone levels with succeeding generations. Morphologically, progression to more
cancer and less secretory activity was noticed.