Effect of the preestrogen 4-androstene-3,17-dion-19-al on the Dunning R3327 prostatic adenocarcinoma.
The purpose of this pilot study was to determine if biogenetic precursors of estrone such as 4-androstene-3,17-dion-19-al, which is virtually devoid of thrombotic potential as well as androgenic and uterotrophic activity, could replace estrogen in the treatment of the hormone-sensitive Dunning R3327 prostatic adenocarcinoma in the male Copenhagen rat. If such were the case, the way would be open to an improved form of palliative therapy of prostatic cancer with the potential for decreased estrogenic side effects and cardiovascular complications. To this end, the R3327 tumor was transplanted (Day 0) into the flank of 10-week-old male Copenhagen rats, and treatment was begun 20 weeks later at which time the tumors reached a mean volume of 2160 cu cm. In addition to 4-androstene-3,17-dion-19-al (1 and 10 mg/day), diethylstilbestrol (33 micrograms/day) and 17 beta-estradiol (3.3 and 33 micrograms/day) were studied (daily for 60 days). At 1 mg/day, 4-androstene-3,17-dion-19-al produced a 43% inhibition of tumor growth (Day 203) while, in the 10 mg/day group, a 72% inhibition of tumor growth was measured on Day 196 (roughly equivalent to that produced by estradiol at 3.3 micrograms/day), with a 50% inhibition on Day 231. It is concluded that the tumor-inhibiting activity of 4-androstene-3,17-dion-19-al, coupled with its very low thrombotic potential, indicated that orally active analogues of this steroid may offer advantages over estrogens in the palliative treatment of prostatic cancer.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
D000735:Androstenedione; D004958:Estradiol; D004054:Diethylstilbestrol; C014142:19-oxo-delta(4) androstene-3,17-dione