A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.

Abstract

Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.

Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer

“…This confirms experience in two similar studies with response rates respectively of 23% (95% CI 12-34%) and 16% (95% CI 12-20%) (Raats et al, 1992;Hoeffken et al, 1992). For second-line endocrine therapy these results may be slightly lower than for some other published reports on aromatase inhibitors, including aminoglutethimide (Powles, 1983;Stuart-Harris and Smith, 1984b;Miller, 1989) and 4-hydroxyandrostenedione (Goss and Gwyn, 1994).…”

“…For second-line endocrine therapy these results may be slightly lower than for some other published reports on aromatase inhibitors, including aminoglutethimide (Powles, 1983;Stuart-Harris and Smith, 1984b;Miller, 1989) and 4-hydroxyandrostenedione (Goss and Gwyn, 1994). The confidence intervals, however, in this study and in the other two (Raats et al, 1992;Hoeffken et al, 1992) are wide, ranging from 9% to 34%. In addition, a comparison of response rates from second-line hormonal therapies used in different studies does not allow conclusions about the 'best second-line hormonal agent' because of possible selection bias, including the number of nonresponders to first-line endocrine therapy (Powles, 1983).…”

“…The design of our study and patient numbers involved do not allow dose -response conclusions to be drawn. Raats et al (1992) conducted a study in which the patients were randomised to receive fadrozole 0.5 mg b.d. or 2 mg b.d.…”

“…In one study, Santen et al (1989) have shown that aldosterone suppression occurred only at substantially higher doses than those required for maximum oestrogen suppression (8 and 16 mg day-'). Two phase II studies did not show a significant difference in toxicity or response between 1 mg day-' and 4 mg day-1 in one study or between 1, 2 and 4 mg day-' in the other study (Raats et al, 1992;Hoeffken et al, 1992). In contrast, our preliminary clinical investigations with this compound indicated that there was a dose-related suppression of oestradiol levels between the doses of 0.6 and 4 mg day-1 and that aldosterone levels were suppressed by approximately 50% at the 4 mg day-1 dose Stein et al, 1990).…”

Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor

“…in the treatment of human breast cancer, and has shown activity against advanced breast cancer in women (Raats et al, 1992) with minimal effects on aldosterone (Demers et al, 1990) and glucocorticoid secretion at daily doses (1-2 mg day ') producing near-maximal suppression of oestrogens (Santen et al, 1989). At higher doses (8 mg day-') fadrozole inhibits basal aldosterone sretion (Demers et al, 1990) and at 16 mg day-' bhlts the plasma corisol response to ACTH but does not alter basal urinary cortisol secretion (Santen et al, 1989).…”