Sasaki Y, Shinkai T, Eguchi K, Tamura T, Ohe Y, Ohmori T, Saijo N
Department of Medical Oncology, National Cancer Center, Tokyo, Japan.
Cancer Chemother Pharmacol. 1991;27(4):263-70. doi: 10.1007/BF00685110.
We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and six NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%-65% and 14%-16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.
我们报告了一种通过生物测定法建立的预测模型，该模型用于预测新型铂类类似物对肺癌的临床反应，此生物测定法使用了包括小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC）在内的人肺癌细胞系。在双琼脂集落形成细胞试验中，将六种不同的SCLC细胞系和六种NSCLC细胞系的指数生长期细胞暴露于三种铂化合物（顺铂、卡铂和254-S）的不同浓度下。SCLC细胞系中顺铂、卡铂和254-S抑制50%集落形成的浓度（IC50值）显著低于NSCLC细胞系。共有15名患者进入了药理学研究。分别给5名患者静脉滴注80mg/m²顺铂、450mg/m²卡铂和100mg/m² 254-S。使用NCI-H-69（SCLC细胞系）和PC-9（NSCLC细胞系）作为靶细胞，通过克隆形成技术进行生物测定以及化学测定。基于患者血浆的抗肿瘤活性，使用抗肿瘤指数（ATI）进行抗肿瘤活性的生物学比较，ATI定义为通过生物测定获得的集落抑制百分比与时间曲线下的面积，并通过梯形法则计算。当使用NCI-H-69和PC-9作为生物测定的靶细胞时，ATI显示出集落抑制活性。根据以下公式，生物测定获得的ATI与化学测定获得的曲线下面积（AUC）相比，与顺铂和卡铂对SCLC和NSCLC的临床反应具有更好的相关性：[报告的反应率（%）]=11.5668 + 0.0014×[ATI]（r = 0.97）。该公式预测254-S对SCLC和NSCLC的反应率分别为40%-65%和14%-16%。前瞻性研究怀疑254-S对SCLC的活性即便不比卡铂更强，至少也与卡铂相同，并且对NSCLC的活性与顺铂几乎相同。
