依西美坦在非甾体类芳香化酶抑制剂经治失败的晚期乳腺癌患者中的临床应用

Activity of exemestane in advanced breast cancer after failure of nonsteroidal aromatase inhibitors

背景与目的:依西美坦为甾体类芳香化酶灭活剂,能不可逆地结合到芳香化酶与雄激素底物的结合位点上,引起酶永久失活,阻断雄激素向雌激素的转化。依西美坦对激素受体阳性绝经后复发转移性乳腺癌具有明显的疗效,且有研究表明,依西美坦与其他内分泌药物包括非甾体类芳香化酶抑制剂之间无明显交叉耐药反应。本研究旨在评价依西美坦在采用非甾体类芳香化酶抑制剂治疗失败的晚期乳腺癌患者中的临床应用价值。方法:33例雌激素(estrogen receptor,ER)和(或)孕激素受体(progesterone receptor,PR)阳性或不明的绝经后晚期乳腺癌患者,且均为既往接受过非甾体类芳香化酶抑制剂治疗进展的患者,口服依西美坦,1次/d,每次25mg,28d为1个周期,评价疗效和不良反应。结果:全组33例患者中,无CR病例,PR2例(6.0%),SD19例(57.6%),其中稳定持续时间≥24周者13例,PD12例(36.4%),有效率(CR+PR)为6.0%,临床获益率(CR+PR+SD≥24周)为45.5%,中位无进展生存期(PFS)为5.9个月(1～29.3个月)。年龄≥60岁患者的临床获益率高于年龄<60岁患者,既往未接受过化疗(不包括辅助化疗)患者出现进展的比例低于接受过化疗患者,差异均有统计学意义(P<0.05)。所有患者均无严重不良反应发生。结论:依西美坦在非甾体类芳香化酶抑制剂治疗失败的绝经后内分泌治疗反应型晚期乳腺癌患者中仍能取得较好的临床疗效。

Background and purpose：Exemestane is a new steroidal aromatase inactivator which can bind irreversibly to the substrate-binding site of the aromatase enzyme,permanently inactivate the enzyme and block the conversion of androgen to estrogen.Exemestane is a potent drug with usages in hormone-receptor positive postmenopausal women with metastatic breast cancer.Previous studies have suggested a lack of clinical cross-resistance between exemestane and other endocrine therapy,including nonsteroidal aromatase inhibitor （AI）.Our study evaluated the antitumor value of exemestane in metastatic breast cancer patients who had the progressive disease after treatment with a nonsteroidal aromatase inhibitor.Methods：Thirty-three estrogen receptor （ER） and/or progesterone receptor （PR） positive or unknown postmenopausal patients with advanced breast cancer,who had progressive disease after treatment with a nonsteroidal aromatase inhibitor,entered this study.Exemestane was administered orally,25mg daily,28 days per cycle.Results：All 33 patients were able to be evaluated for efficacy and adverse effects.There were no complete responses （CR）,there were 2 （6.0%） partial responses （PR）,19 （57.6%） with stable disease （SD）,13 with SD≥24 weeks and 12（36.4%） with progressive disease （PD）.The objective response rate （CR＋PR） was 6.0% and overall clinical benefit （CR＋PR＋SD≥24 weeks） was 45.5%.The median progression free survival （PFS） was 5.9 months （129.3 months）.Patients older than 60 years of age had a higher overall clinical benefit than the younger patients.Patients without previous chemotherapy for advanced disease were less likely to progress than those who previously underwent chemotherapy.These differences had statistic significance （P〈0.05）.No severe side effects appeared in any of the patients.Conclusion：Exemestane is an effective therapy after third-generation non-steroidal aromatase inhibitor failed in post-menopausal endocrine-responsive metastatic breast cancer.