Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in healthy postmenopausal women.
We have performed a phase I study of the effect of a single dose of CGS 20267, an oral nonsteroidal aromatase inhibitor, in 12 healthy volunteer postmenopausal women. Each subject received 2 single doses of CGS 20267 (0.1, 0.5, or 2.5 mg) or placebo separated by a washout period of at least 6 weeks. There was statistically significant suppression of serum estrone and estradiol at all three doses of CGS 20267 tested. Serum estrone and estradiol concentrations were maximally suppressed by 76% and 79% from baseline levels, respectively. Urinary excretion of estrone and estradiol was also suppressed, although this did not reach statistical significance. Serum concentrations of aldosterone, cortisol, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, FSH, LH, and TSH were unaffected by CGS 20267. The drug was well tolerated, with no significant side-effects. This study has shown CGS 20267 to be a potent and specific aromatase inhibitor, and further studies are now needed to assess its clinical efficacy.
Iveson
T J
TJ
Breast Unit, Royal Marsden Hospital, London, United Kingdom.
Smith
I E
IE
Ahern
J
J
Smithers
D A
DA
Trunet
P F
PF
Dowsett
M
M
D019326:17-alpha-Hydroxyprogesterone; D000284:Administration, Oral; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000735:Androstenedione / Q000097:blood; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood* / Q000652:urine; D004970:Estrone / Q000097:blood* / Q000652:urine; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D000077289:Letrozole; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008593:Menopause; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011897:Random Allocation; D013739:Testosterone / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D006908:Hydroxyprogesterones; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D000450:Aldosterone; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone; D000077289:Letrozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D006854:Hydrocortisone