TY - JOUR
T1 - The minimal effective exemestane dose for endocrine activity in advanced breast cancer
AU - Bajetta, E.
AU - Zilembo, N.
AU - Noberasco, C.
AU - Martinetti, A.
AU - Mariani, L.
AU - Ferrari, L.
AU - Buzzoni, R.
AU - Greco, M.
AU - Bartoli, C.
AU - Spagnoli, I.
AU - Danesini, G. M.
AU - Artale, S.
AU - Paolini, J.
PY - 1997/4
Y1 - 1997/4
N2 - 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.
AB - 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.
KW - advanced disease
KW - aromatase inhibitor
KW - breast cancer
KW - hormonotherapy
KW - postmenopause
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U2 - 10.1016/S0959-8049(96)00494-7
DO - 10.1016/S0959-8049(96)00494-7
M3 - Article
C2 - 9274439
AN - SCOPUS:0030919160
VL - 33
SP - 587
EP - 591
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 4
ER -