Wolff S N, Grosh W W, Prater K, Hande K R
Cancer Chemother Pharmacol. 1987;19(3):246-9. doi: 10.1007/BF00252980.
VP-16-213 (Etoposide) is an active antineoplastic agent which has undergone extensive evaluation of clinical dose escalation. To corroborate a putative dose-response relationship, we studied, in a modified clonogenic assay, various doses and durations of exposure. VP-16-213 at doses of 0.01, 0.05, 0.10, 0.50, 1.0, 5.0, and 10.0 micrograms/ml, each with exposure durations of 1, 3, 18, and 30 h, was studied in vitro against two human tumor cell lines, MOLT and 9812. The doses and durations of exposure were chosen to approximate some of the pharmacokinetic values achievable in either standard-dose or high-dose clinical studies. The results, summarized as linear regression lines, demonstrate with statistical significance (p less than 0.03) that there is correlation between dose and cytotoxicity and between dose X duration of exposure (representing the area under the concentration-time curve) and cytotoxicity. Our in vitro data thus support the concept of intensive use of VP-16-213 to maximize antitumor activity. However, how best to accomplish the manipulation of dose and duration of exposure is not yet clear and will be the subject of future clinical investigations.
VP - 16 - 213（依托泊苷）是一种活性抗肿瘤药物，已对其临床剂量递增进行了广泛评估。为了证实假定的剂量反应关系，我们在改良的克隆形成试验中研究了不同剂量和暴露持续时间。以0.01、0.05、0.10、0.50、1.0、5.0和10.0微克/毫升的剂量，分别给予1、3、18和30小时的暴露持续时间，在体外研究了VP - 16 - 213对两种人类肿瘤细胞系MOLT和9812的作用。选择这些剂量和暴露持续时间是为了接近在标准剂量或高剂量临床研究中可达到的一些药代动力学值。结果总结为线性回归线，具有统计学意义（p小于0.03），表明剂量与细胞毒性之间以及剂量×暴露持续时间（代表浓度 - 时间曲线下面积）与细胞毒性之间存在相关性。因此，我们的体外数据支持强化使用VP - 16 - 213以最大化抗肿瘤活性的概念。然而，如何最好地实现剂量和暴露持续时间的调整尚不清楚，这将是未来临床研究的主题。
