Tamoxifen - What next?
Tamoxifen - What next?
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DOI：
10.1634/theoncologist.9-4-378
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发表时间：
2004-01-01
期刊：
影响因子：
5.8
通讯作者：
Gradishar, WJ
中科院分区：
文献类型：
--
作者：
Gradishar, WJ
大多数晚期乳腺癌（ABC）患者最终因疾病进展而死亡。因此，ABC 的治疗本质上主要是姑息性的，因此特定治疗的耐受性与这些患者特别相关。虽然细胞毒性化疗和内分泌治疗在激素敏感的晚期疾病中表现出疗效，但内分泌治疗将疗效与最小的急性毒性结合起来。 20 多年来，他莫昔芬一直被选为绝经后、激素敏感型 ABC 的内分泌治疗药物。最近，推出了与他莫昔芬具有不同作用机制的新内分泌药物。有证据表明，芳香酶抑制剂阿那曲唑（Arimidex®；阿斯利康；威尔明顿，特拉华州）、来曲唑（Femara®；诺华制药公司；新泽西州东汉诺威）和依赛坦（Aromasin®；Pharmacia Corp.；Peapack，新泽西州）在一线治疗绝经后、激素敏感 ABC。类似地，在他莫昔芬失败后，氟维司群（Faslodex(R)；阿斯利康）是一种新型雌激素受体（ER）拮抗剂，可下调 ER，至少与阿那曲唑一样有效，耐受性良好，并且与他莫昔芬不存在交叉耐药性。与他莫昔芬不同，氟维司群没有已知的激动剂作用。连续使用此类药物可以延长内分泌治疗的使用时间，从而避免与细胞毒性化疗相关的更严重的毒性。事实上，一系列研究表明，这种顺序使用是一种相关、积极且耐受性良好的选择。建立纳入新型内分泌药物的比较疗效和最佳序列对于确定激素治疗在 ABC 中的未来作用至关重要；这项工作的结果将决定他莫昔芬在快速变化的治疗环境中的相对地位。
Most patients with advanced breast cancer (ABC) ultimately die due to disease progression. Consequently, treatments for ABC are predominantly palliative in nature and, therefore, the tolerability profile of a given treatment is particularly relevant in these patients. While cytotoxic chemotherapy and endocrine therapy exhibit efficacy in hormone-sensitive, advanced disease, it is endocrine therapy that combines efficacy with minimal acute toxicity. Tamoxifen has been the chosen endocrine therapy for postmenopausal, hormone-sensitive, ABC for over 20 years. More recently, new endocrine agents with different mechanisms of action from tamoxifen have been introduced. Evidence indicates that the aromatase inhibitors anastrozole (Arimidex(R); AstraZeneca; Wilmington, DE), letrozole, (Femara(R); Novartis Pharmaceuticals Corp.; East Hanover, NJ) and exernestane (Aromasin(R); Pharmacia Corp.; Peapack, NJ) offer superior efficacy and tolerability to tamoxifen in the first-line treatment of postmenopausal, hormone-sensitive ABC. Similarly, after tamoxifen failure, fulvestrant (Faslodex(R); AstraZeneca), a new estrogen receptor (ER) antagonist that downregulates the ER, is at least as effective as anastrozole, is well tolerated, and is not cross-resistant with tamoxifen. Unlike tamoxifen, fulvestrant has no known agonist effects. The sequential use of such agents may prolong the time during which endocrine therapies can be used, thereby avoiding the more acute toxicities associated with cytotoxic chemotherapy. Indeed, a series of studies has shown that this sequential use is a relevant, active, and well-tolerated option. Establishing the comparative efficacies and optimal sequences that incorporate the newer endocrine agents will be central in determining the future role of hormonal therapy in ABC; the results of this work will determine the relative place of tamoxifen in what is a rapidly changing therapeutic environment.