Kuroiwa S, Maruyama S, Okada M, Abe F
Dept. of Anticancer Drugs, Nippon Kayaku Co., Ltd.
Gan To Kagaku Ryoho. 1998 Aug;25(10):1581-9.
Toremifene (TOR) is a new antiestrogenic agent, a triphenylethylene derivative that was developed as an alternative to tamoxifene (TAM). TOR has been observed to be more effective than TAM with milder toxicity at high doses. We examined the in vitro combination-effect of TOR with cyclophosphamide, adriamycin, 5-fluorouracil and three drug mixture (CAF) on the growth of various human mammary carcinomas. The combination shows a semi-additive or additive growth inhibitory effect on all estrogen positive cells used here except one cell line. In particular, the additive or synergic combination-effect was observed on TAM resistant cells. Furthermore, TOR exhibits a chemosensitizing activity in ADR-resistant cells by expressing P-glycoprotein coded by MDR-1 (multidrug resistance gene). The chemosensitizing activity is dose-dependent of TOR. As described above, the combination of TOR with CAF shows more than a semi-additive effect in this experiment. In conclusion, the addition of high-dose TOR to CAF therapy might be useful for advanced/recurrent breast cancer.
托瑞米芬（TOR）是一种新型抗雌激素药物，是一种三苯乙烯衍生物，开发出来作为他莫昔芬（TAM）的替代品。已观察到TOR在高剂量时比TAM更有效且毒性更轻。我们研究了TOR与环磷酰胺、阿霉素、5-氟尿嘧啶以及三种药物混合物（CAF）对各种人类乳腺癌生长的体外联合效应。该联合对除一种细胞系外的所有此处使用的雌激素阳性细胞均显示出半相加或相加的生长抑制作用。特别是，在对TAM耐药的细胞上观察到了相加或协同的联合效应。此外，TOR通过表达由多药耐药基因（MDR-1）编码的P-糖蛋白，在对阿霉素耐药的细胞中表现出化学增敏活性。化学增敏活性与TOR的剂量相关。如上所述，在本实验中TOR与CAF的联合显示出超过半相加的效应。总之，在CAF治疗中添加高剂量TOR可能对晚期/复发性乳腺癌有用。
