Formestane (4-hydroxyandrostenedione) is an effective and competitive inhibitor of
aromatase, the
enzyme responsible for the conversion of
androgens to
estrone and
estradiol. Significant reductions in plasma
estradiol levels are observed following intramuscular administration of
formestane to postmenopausal women with advanced metastatic
breast cancer. Overall response rates to intramuscular
formestane in these patients are approximately 25 to 30% and a further 20 to 30% of patients experience disease stabilisation during treatment. Response rates are improved in patients with
hormone responsive tumours and in those who have responded to previous endocrine
therapy. Soft tissue
metastases generally show the best response to
formestane treatment while visceral
metastases (in particular liver) show a poor response. The median duration of response is usually between 7 months and 1 year.
Formestane has been generally well tolerated in the relatively small clinical trials conducted to date with adverse effects reported in approximately 13% of patients following intramuscular administration. The most frequent adverse effects are local reactions at the injection site and systemic effects mainly related to the effect of the
drug on the hormonal milieu. Thus,
formestane is effective as a second-line endocrine treatment for advanced metastatic
breast cancer in women with natural or artificially induced menopause, with apparent tolerability advantages over older agents such as
aminoglutethimide; with wider study and experience it may yet challenge
tamoxifen as a first-line endocrine
therapy in metastatic
breast cancer.