Formestane. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of breast cancer and prostatic cancer.

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.