Celio L, Martinetti A, Ferrari L, Buzzoni R, Mariani L, Miceli R, Seregni E, Procopio G, Cassata A, Bombardieri E, Bajetta E
Medical Oncology B Division, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Anticancer Res. 1999 May-Jun;19(3B):2261-8.
The combination of a GnRH analogue and an aromatase inhibitor can induce a complete estrogen blockade in premenopausal breast cancer patients.
Twenty-one premenopausal women with advanced breast cancer were randomised to receive the GnRH analog triptorelin (3.75 mg i.m. monthly; n = 10) alone or in combination with the aromatase inhibitor formestane (4-OHA, 500 mg i.m. fortnightly; n = 11) to compare the effect of both treatments on the patients' estrogenic milieu. Therefore, serum estrogen, gonadotropin and sex hormone-binding globulin (SHBG) levels were investigated before the start of treatment and subsequently over a three-month period.
There was a significant between-group difference in estrogen suppression during therapy. In comparison with baseline values, after four weeks of treatment the estradiol levels decreased by an average of 86.9% (95% CI, 70.5-94.2%) in the group treated with triptorelin alone and by 97.3% (95% CI, 94.1-98.8%; P = 0.0422) in the combination group; the respective figures for estrone were 48.5% (95% CI, 27.5-63.5%) and 70.4% (95% CI, 52.3-81.6%; P = 0.0007) and for estrone sulfate 56.7% (95% CI, 40-68.8%) and 80.5% (95% CI, 69.4-87.6%; P = 0.0055). No difference was observed between the groups in terms of gonadotropin suppression; both treatment modalities led to a slight but delayed decrease in SHBG levels. Three of the patients treated with triptorelin alone experienced tumor regression compared with four patients in the combination group. No appreciable side effects of the combination therapy were observed.
The treatment of premenopausal patients with triptorelin plus 4-OHA is feasible and leads to a much greater inhibition of main circulating estrogens than treatment with the analog alone. Since the combination of a GnRH analog and an aromatase inhibitor might potentially enhance the anti-tumor efficacy of the analog alone owing to more favorable endocrine effects, such a therapeutic approach deserves more extensive evaluation in the clinical setting.
促性腺激素释放激素（GnRH）类似物与芳香化酶抑制剂联合使用可在绝经前乳腺癌患者中诱导完全的雌激素阻断。
21例绝经前晚期乳腺癌患者被随机分为两组，一组单独接受GnRH类似物曲普瑞林（每月肌肉注射3.75mg；n = 10），另一组接受曲普瑞林联合芳香化酶抑制剂福美坦（4-羟基雄烯二酮，每两周肌肉注射500mg；n = 11），以比较两种治疗方法对患者雌激素环境的影响。因此，在治疗开始前及随后的三个月内对血清雌激素、促性腺激素和性激素结合球蛋白（SHBG）水平进行了研究。
治疗期间两组在雌激素抑制方面存在显著差异。与基线值相比，单独使用曲普瑞林治疗组在治疗四周后雌二醇水平平均下降86.9%（95%可信区间，70.5 - 94.2%），联合治疗组下降97.3%（95%可信区间，94.1 - 98.8%；P = 0.0422）；雌酮的相应数据分别为48.5%（95%可信区间，27.5 - 63.5%）和70.4%（95%可信区间，52.3 - 81.6%；P = 0.0007），硫酸雌酮分别为56.7%（95%可信区间，40 - 68.8%）和80.5%（95%可信区间，69.4 - 87.6%；P = 0.0055）。两组在促性腺激素抑制方面未观察到差异；两种治疗方式均导致SHBG水平轻微但延迟下降。单独使用曲普瑞林治疗的患者中有3例出现肿瘤消退，联合治疗组有4例。联合治疗未观察到明显的副作用。
曲普瑞林加4-羟基雄烯二酮治疗绝经前患者是可行的，与单独使用类似物相比，能更有效地抑制主要循环雌激素。由于GnRH类似物与芳香化酶抑制剂联合使用可能因更有利的内分泌效应而潜在增强单独使用类似物的抗肿瘤疗效，这种治疗方法值得在临床环境中进行更广泛的评估。
