Second line endocrine treatment of postmenopausal advanced breast cancer. Preliminary endocrine results of a 5-arm randomized phase II trial of medium vs low dose aminoglutethimide, with or without hydrocortisone vs hydrocortisone alone (EORTC 10861).
The supposed mechanism of action of aminoglutethimide (AG), medical adrenalectomy, has been challenged. AG is now considered to act as an inhibitor of the aromatization of mainly adrenal androgens to estrogens in peripheral tissues and/or breast cancer itself. To further establish the AG dose required to sufficiently reduce estrogen levels in plasma and the possible role of hydrocortisone (HC) in combination with AG or by itself, postmenopausal advanced breast cancer patients received AG low (125 mg bid) or medium (250 mg bid) dose alone or combined with HC (20 mg bid) or HC alone (20 mg bid). Preliminary hormonal data show a similar reduction of serum estrone and estrone sulphate by at least some 50% at 8 wk in all treatment groups. At 6 months these effects persist except for patients treated with HC alone. In the latter a normalization of estrone levels is observed with effective suppression of adrenal androgen precursors, suggesting increased aromatase activity with prolonged glucocorticoid treatment.
Bruning
P F
PF
The Netherlands Cancer Institute, Amsterdam.
Bonfrèr
J M
JM
Wildiers
J
J
Jassem
J
J
Beex
L V
LV
Schornagel
J
J
Nooijen
W J
WJ
D000616:Aminoglutethimide / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*
D005938:Glucocorticoids; D000616:Aminoglutethimide; D004970:Estrone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D001141:Aromatase; C017296:estrone sulfate; D006854:Hydrocortisone