Abe R, Sawano A, Ueki H, Akimoto M, Kimura M
Gan To Kagaku Ryoho. 1987 Mar;14(3 Pt 2):785-92.
The clinical response rate of chemotherapy or endocrine therapy for advanced or recurrent breast cancer has been described as being about 30%, regardless of steroid hormone status. However, the response rate for endocrine therapy is about double in patients with positive estrogen receptor. In order to obtain a higher response rate than that for single therapy, experimental attempts were made to combine cytotoxic agents, antiestrogenic agents, ablative therapy and immunotherapy from the viewpoints of tumor cell kinetics, natural killer activity and interferon activity of spleen cells. Tamoxifen and orchiectomy were shown by flow cytometry to produce a G1 block, increasing the G0, G1 phase and decreasing the S phase, in MCF-7 cells in vitro and in SC 115 cells, in vivo respectively, for a long period. On the other hand, 5-FU showed most effective cytotoxicity in the S phase of both types of tumor cells in vitro and in vivo, although the depressed S phase recovered within 24 hours. Therefore, any combined chemo-endocrine therapy should be devised so that the endocrine therapy maintains a G1 block for a long period and performed immediately following chemotherapy during the decreased S phase of the tumor cells. N K activity of spleen cells were enhanced, and interferon production in spleen cells was not changed by ovariectomy in C3H/He mice compared with sham-operated mice. It is suggested that endocrine therapy may affect the immunopotentiality of cancer patients.
晚期或复发性乳腺癌化疗或内分泌治疗的临床缓解率约为30%，与类固醇激素状态无关。然而，雌激素受体阳性患者内分泌治疗的缓解率约为前者的两倍。为了获得比单一治疗更高的缓解率，从肿瘤细胞动力学、脾细胞自然杀伤活性和干扰素活性的角度出发，进行了将细胞毒性药物、抗雌激素药物、消融治疗和免疫治疗联合应用的实验尝试。通过流式细胞术显示，他莫昔芬和睾丸切除术分别在体外MCF-7细胞和体内SC 115细胞中产生G1期阻滞，使G0、G1期增加，S期减少，并持续较长时间。另一方面，5-氟尿嘧啶在体外和体内对两种肿瘤细胞的S期均显示出最有效的细胞毒性，尽管降低的S期在24小时内恢复。因此，任何联合化疗-内分泌治疗方案的设计都应使内分泌治疗长期维持G1期阻滞，并在肿瘤细胞S期减少期间化疗后立即进行。与假手术小鼠相比，C3H/He小鼠卵巢切除术后脾细胞的NK活性增强，脾细胞中干扰素的产生没有变化。提示内分泌治疗可能影响癌症患者的免疫潜能。
