FORMESTANE - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND CLINICAL EFFICACY IN THE TREATMENT OF POSTMENOPAUSAL BREAST-CANCER

Formestane (4-hydroxyandrostenedione) is an aromatase inhibitor which significantly reduces plasma levels of estrogen and has shown antitumo ur activity in postmenopausal women with breast cancer. Objective resp onse rates in heavily pretreated patients with advanced breast cancer generally range between 20 and 30% during treatment with intramuscular formestane 250 or 500 mg once every 2 weeks, and a further 20 to 30% of patients experience disease stabilisation. The median duration of r esponse is between 8 and 14 months. Highest response rates are observe d in soft tissue metastases, in patients with estrogen-responsive rumo urs and in those showing a response to previous endocrine therapy. Fur thermore, there is some evidence to suggest that higher response rates are achieved with formestane 500 versus 250 mg once every 2 weeks. In comparative studies, the clinical efficacy of intramuscular formestan e 250 mg did not differ significantly from that of oral megestrol when administered as second-line endocrine therapy to patients with advanc ed disease in whom previous tamoxifen therapy had failed. In addition, formestane produced a response rate, duration of response and overall survival rate that was not significantly different from that of oral tamoxifen when administered as first-line endocrine therapy to patient s with advanced disease, bur tamoxifen was superior in some measures. Further investigation of these 2 agents, including the higher dosage o f formestane (500 mg), is necessary to confirm their relative efficaci es. Formestane is well tolerated by the majority of patients; adverse events rarely necessitate cessation of therapy. The most common advers e events are local reactions at the injection site and systemic events usually related to the effect of the drug on the hormonal milieu. The systemic tolerability of formestane is similar to that of tamoxifen b ur better than that of megestrol. Thus, formestane is effective and we ll tolerated as first-line endocrine therapy for advanced disease. How ever at present, it is unlikely to challenge tamoxifen in this indicat ion based on recent findings from a large comparative study and the fa ct that formestane requires intramuscular administration. Nonetheless, formestane, which appears to have a better tolerability profile than other currently available second-line agents (including megestrol and the aromatase inhibitor aminoglutethimide), is a valuable drug for the second-line treatment of postmenopausal women with advanced breast ca ncer.