Russell J, Adam J, Wheldon T E, Kaye S B
Radiation Oncology Research Group, Beatson Oncology Centre, Belvidere Hospital, Glasgow, Scotland.
Cancer Chemother Pharmacol. 1989;23(2):111-4. doi: 10.1007/BF00273527.
We compared cisplatin (cis-DDP) and two of its analogues, carboplatin (JM8, CBDCA) and iproplatin (JM9, CHIP) for their ability to retard the growth of multicellular tumour spheroids. The spheroids were derived from two human tumours, a neuroblastoma and a non-small-cell lung cancer. To produce a given level of regrowth delay in lung cancer spheroids, carboplatin and iproplatin were required at concentrations approximately 10 times that of cis-DDP. In the neuroblastoma spheroid experiments, iproplatin and cis-DDP produced the same level of regrowth delay when iproplatin was present at a concentration greater than 10 times that of cis-DDP. Carboplatin also required much higher concentrations than cis-DDP to produce equivalent regrowth delay in neuroblastoma. The dose-response curve produced by carboplatin on neuroblastoma spheroids displayed a pronounced shoulder in the low-dose region; this phenomenon was not seen with cis-DDP. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of lung cancer, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with cis-DDP. However, one must be cautious about generalizing on the basis of results from only two cell lines as well as applying in vitro data to clinical situations.
我们比较了顺铂（顺式二氨基二氯铂）及其两种类似物卡铂（JM8，环丁二羧酸二氨合铂）和异丙铂（JM9，氯异柠檬酸铂）抑制多细胞肿瘤球体生长的能力。这些球体来源于两种人类肿瘤，一种是神经母细胞瘤，另一种是非小细胞肺癌。为了在肺癌球体中产生给定水平的再生长延迟，所需的卡铂和异丙铂浓度约为顺铂的10倍。在神经母细胞瘤球体实验中，当异丙铂的浓度大于顺铂浓度的10倍时，异丙铂和顺铂产生相同水平的再生长延迟。在神经母细胞瘤中，卡铂也需要比顺铂高得多的浓度才能产生等效的再生长延迟。卡铂对神经母细胞瘤球体产生的剂量反应曲线在低剂量区域显示出明显的平台期；顺铂未出现这种现象。这些发现可能对这些药物的临床应用有影响，特别是支持卡铂在肺癌治疗中的作用，因为患者对卡铂的总游离药物暴露量可能比顺铂高出多达16倍。然而，仅根据两种细胞系的结果进行概括以及将体外数据应用于临床情况时必须谨慎。
