Wiseman L R, Goa K L
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1996 Oct;9(4):292-306. doi: 10.2165/00002512-199609040-00006.
Formestane (4-hydroxyandrostenedione) is an aromatase inhibitor which significantly reduces plasma levels of estrogen and has shown antitumour activity in postmenopausal women with breast cancer. Objective response rates in heavily pretreated patients with advanced breast cancer generally range between 20 and 30% during treatment with intramuscular formestone 250 or 500mg once every 2 weeks, and a further 20 to 30% of patients experience disease stabilisation. The median duration of response is between 8 and 14 months. Highest response rates are observed in soft tissue metastases, in patients with estrogen-responsive tumours and in those showing a response to previous endocrine therapy. Furthermore, there is some evidence to suggest that higher response rates are achieved with formestane 500 versus 250mg once every 2 weeks. In comparative studies, the clinical efficacy of intramuscular formestane 250mg did not differ significantly from that of oral megestrol when administered as second-line endocrine therapy to patients with advanced 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 patients with advanced disease, but tamoxifen was superior in some measures. Further investigation of these 2 agents, including the higher dosage of formestane (500mg), is necessary to confirm their relative efficacies. Formestane is well tolerated by the majority of patients; adverse events rarely necessitate cessation of therapy. The most common adverse 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 but better than that of megestrol. Thus, formestane is effective and well tolerated as first-line endocrine therapy for advanced disease. However, at present, it is unlikely to challenge tamoxifen in this indication, based on recent findings from a large comparative study and the fact 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 cancer.
福美司坦（4-羟基雄烯二酮）是一种芳香化酶抑制剂，可显著降低血浆雌激素水平，并已在绝经后乳腺癌女性中显示出抗肿瘤活性。对于既往接受过大量治疗的晚期乳腺癌患者，每2周肌内注射250或500mg福美司坦治疗期间，客观缓解率一般在20%至30%之间，另有20%至30%的患者病情稳定。缓解持续时间中位数为8至14个月。在软组织转移患者、雌激素反应性肿瘤患者以及对既往内分泌治疗有反应的患者中观察到最高缓解率。此外，有一些证据表明，每2周一次使用500mg福美司坦比250mg能获得更高的缓解率。在比较研究中，当对既往他莫昔芬治疗失败的晚期疾病患者进行二线内分泌治疗时，肌内注射250mg福美司坦的临床疗效与口服甲地孕酮无显著差异。此外，当对晚期疾病患者进行一线内分泌治疗时，福美司坦产生的缓解率、缓解持续时间和总生存率与口服他莫昔芬无显著差异，但在某些指标上他莫昔芬更具优势。对这两种药物（包括更高剂量的福美司坦（500mg））进行进一步研究，以确认它们的相对疗效是必要的。大多数患者对福美司坦耐受性良好；不良事件很少需要停止治疗。最常见的不良事件是注射部位的局部反应和通常与药物对激素环境的影响相关的全身事件。福美司坦的全身耐受性与他莫昔芬相似，但优于甲地孕酮。因此，福美司坦作为晚期疾病的一线内分泌治疗有效且耐受性良好。然而，基于一项大型比较研究的最新发现以及福美司坦需要肌内注射这一事实，目前它在该适应症中不太可能挑战他莫昔芬。尽管如此，福美司坦似乎比其他目前可用的二线药物（包括甲地孕酮和芳香化酶抑制剂氨鲁米特）具有更好的耐受性，是绝经后晚期乳腺癌女性二线治疗的一种有价值的药物。
