Budman Daniel R, Calabro Anthony
Don Monti Division of Oncology, North Shore University Hospital, New York University School of Medicine, Manhasset 11030, USA.
Breast Cancer Res Treat. 2002 Jul;74(1):41-6. doi: 10.1023/a:1016070230538.
The use of combination chemotherapy is the accepted standard for most human malignancies but little attention has been paid to drug interactions. A combination of drugs may be synergistic, additive, or antagonistic in cytotoxic activity. This study evaluated combinations of agents with docetaxel, one of the most active agents in human breast cancer, using a median effects model to look at synergy or antagonism in vitro as a potential predictor of clinical outcome. Three human breast cancer cell lines, MCF7/wt, MCF7/adr (multiply drug resistant), and BT474 were grown to confluence, plated into 96 well dishes, and incubated with combinations of drugs for 72h. Cytotoxic effect was measured by the MTT assay. Median effect analysis was used to calculate the combination index (CI) with values less than 1 indicating synergism, 1 additive effects, and greater than 1 antagonism. Potentially useful combinations for clinical study which were identified included docetaxel with vinorelbine, docetaxel with dexrazoxane, docetaxel with cis-retinoic acid, docetaxel with disulfiram and either doxorubicin or epirubicin, and docetaxel with dexrazoxane and epirubicin.
联合化疗的应用是大多数人类恶性肿瘤公认的标准治疗方法，但药物相互作用却很少受到关注。联合使用的药物在细胞毒性活性方面可能具有协同、相加或拮抗作用。本研究使用中位效应模型评估了与多西他赛（人类乳腺癌中最有效的药物之一）联合用药的情况，以观察体外的协同或拮抗作用，作为临床结果的潜在预测指标。三种人乳腺癌细胞系，MCF7/wt、MCF7/adr（多重耐药）和BT474，培养至汇合状态，接种到96孔板中，并与联合药物孵育72小时。通过MTT法测定细胞毒性作用。采用中位效应分析来计算联合指数（CI），CI值小于1表示协同作用，等于1表示相加作用，大于1表示拮抗作用。已确定的可能对临床研究有用的联合用药方案包括多西他赛与长春瑞滨、多西他赛与右丙亚胺、多西他赛与顺式维甲酸、多西他赛与双硫仑以及阿霉素或表柔比星，以及多西他赛与右丙亚胺和表柔比星。
