The minimal effective exemestane dose for endocrine activity in advanced breast cancer.
Phase I studies have demonstrated that exemestane, an irreversible oral aromatase inhibitor, is able to suppress circulating oestrogen levels. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to identify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses starting from day 7; the degree of inhibition versus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and LH levels was observed for all doses. Treatment tolerability was satisfactory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulating oestrogens.
Bajetta
E
E
Division of Medical Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Zilembo
N
N
Noberasco
C
C
Martinetti
A
A
Mariani
L
L
Ferrari
L
L
Buzzoni
R
R
Greco
M
M
Bartoli
C
C
Spagnoli
I
I
Danesini
G M
GM
Artale
S
S
Paolini
J
J
D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003864:Depression, Chemical; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C056516:exemestane; C017296:estrone sulfate