PREDICTION OF THE ANTITUMOR-ACTIVITY OF NEW PLATINUM ANALOGS BASED ON THEIR EXVIVO PHARMACODYNAMICS AS DETERMINED BY BIOASSAY
PREDICTION OF THE ANTITUMOR-ACTIVITY OF NEW PLATINUM ANALOGS BASED ON THEIR EXVIVO PHARMACODYNAMICS AS DETERMINED BY BIOASSAY
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DOI：
10.1007/bf00685110
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发表时间：
1991-01-01
影响因子：
3
通讯作者：
SAIJO, N
中科院分区：
文献类型：
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作者：
SASAKI, Y;SHINKAI, T;SAIJO, N
我们通过使用人类肺癌细胞系（包括小细胞（SCLC）和非小细胞肺癌（NSCLC））进行生物测定，报告了新型铂类似物对肺癌临床反应的预测模型。 在双琼脂集落形成细胞测定中，将六种不同 SCLC 和六种 NSCLC 系的呈指数生长的细胞暴露于不同浓度的三种铂化合物（顺铂、卡铂和 254-S）。 顺铂、卡铂和254-S在SCLC细胞系中抑制50%集落形成的浓度（IC50值）显着低于NSCLC细胞系中的浓度。 共有15名患者进入药理学研究。 总计，5 名患者每人静脉滴注 80 mg/m2 254-S。 使用NCI-H-69（SCLC细胞系）和PC-9（NSCLC细胞系）作为靶细胞，通过克隆形成技术实现生物测定和化学测定。 抗肿瘤活性的生物学比较是在患者血浆的抗肿瘤活性的基础上使用抗肿瘤指数（ATI）进行的，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，并按梯形法则计算。 当 NCI-H-69 和 PC-9 用作生物测定的靶细胞时，ATI 揭示了集落抑制活性。 根据以下方程，通过生物测定获得的 ATI 比通过化学测定获得的 AUC 与顺铂和卡铂针对 SCLC 和 NSCLC 的临床反应具有更好的相关性：[报告反应 (%)] = 11.5668 + 0.0014 x [ATI] (r = 0.97)。 通过该公式预测 254-S 针对 SCLC 和 NSCLC 的缓解率分别为 40% - 65% 和 14% - 16%。 预期254-S对于SCLC具有与卡铂相同甚至更高的活性，并且对于NSCLC具有与顺铂几乎相同的活性。
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 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.