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Drugs. 2017 Dec;77(18):2037-2048. doi: 10.1007/s40265-017-0849-3.
A 1-month formulation of the gonadotrophin-releasing hormone agonist (GnRHa) triptorelin (Decapeptyl) has been approved in the EU as an adjuvant treatment in combination with tamoxifen or an aromatase inhibitor (AI), of endocrine-responsive, early-stage breast cancer in women at high risk of recurrence who are confirmed as premenopausal after completion of chemotherapy. This indication reflects the results of the 5-year SOFT and TEXT studies, especially SOFT, in which ovarian function suppression (OFS; mainly achieved with triptorelin) added to tamoxifen provided a significant benefit in the overall study population of premenopausal patients only after adjusting for prognostic factors. It emerged that adding OFS to tamoxifen produced more pronounced benefits in terms of disease control and, furthermore, increased overall survival in the cohort of higher-risk patients who had previously received chemotherapy. Also, compared with tamoxifen alone, the combination of OFS plus exemestane produced more pronounced benefits in terms of disease control than OFS plus tamoxifen. OFS induces premature menopause; when combined with either tamoxifen or exemestane, it increased the endocrine symptom burden. Nonetheless, the two combinations had distinct tolerability profiles (e.g. vasomotor symptoms and thromboembolic events were more frequent with OFS plus tamoxifen, whereas musculoskeletal symptoms, decreased libido, osteoporosis and fractures were more frequent with OFS plus exemestane). Thus, the combinations of OFS (with triptorelin) plus either tamoxifen or an AI are valid options for the adjuvant treatment of endocrine-responsive, early-stage breast cancer in women at sufficiently high risk of relapse to warrant receiving chemotherapy and who remain premenopausal thereafter. Individualized weighing of the potential benefits and adverse effects of treatment is required.
一种戈那瑞林激素激动剂(GnRHa)曲普瑞林(Decapeptyl)的 1 个月配方已在欧盟获得批准,可与他莫昔芬或芳香化酶抑制剂(AI)联合用于辅助治疗,适用于化疗后确认绝经前的内分泌敏感早期乳腺癌、且复发风险高的女性。这一适应证反映了 SOFT 和 TEXT 研究的 5 年结果,尤其是 SOFT 研究结果,其中卵巢功能抑制(OFS;主要通过曲普瑞林实现)联合他莫昔芬治疗绝经前患者总体研究人群在调整预后因素后仅显示出显著获益。结果表明,OFS 联合他莫昔芬在疾病控制方面的获益更为显著,而且对于先前接受过化疗的高危患者亚组,还增加了总体生存率。此外,与他莫昔芬单药治疗相比,OFS 联合依西美坦在疾病控制方面的获益更为显著,而不是 OFS 联合他莫昔芬。OFS 诱导提前绝经;与他莫昔芬或依西美坦联合使用时,会增加内分泌症状负担。尽管如此,这两种联合方案具有不同的耐受性特征(例如,OFS 联合他莫昔芬时更常出现血管舒缩症状和血栓栓塞事件,而 OFS 联合依西美坦时更常出现肌肉骨骼症状、性欲下降、骨质疏松症和骨折)。因此,OFS(与曲普瑞林联用)联合他莫昔芬或 AI 是用于辅助治疗内分泌敏感早期乳腺癌的有效选择,适用于复发风险高到需要接受化疗且此后仍保持绝经前状态的女性。需要对治疗的潜在益处和不良反应进行个体化权衡。