In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers
In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers
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DOI：
10.1006/gyno.1998.5140
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发表时间：
1998-11-01
影响因子：
4.7
通讯作者：
Salmon, SE
中科院分区：
文献类型：
--
作者：
Monk, BJ;Alberts, DS;Salmon, SE
Objective.比较奈达铂（一种研究性铂类似物）与顺铂和卡铂对未经治疗患者的新鲜宫颈癌的体外细胞毒性。在放射治疗或根治性手术前从20名局部浸润性宫颈癌患者中获得样本，在琼脂中培养单细胞悬液后，使用集落计数和[H-3]胸苷掺入来测量细胞毒性，在1和10 μ g/ml剂量水平下测试奈达铂和顺铂，而在10和100 μ g/ml剂量水平下连续测试卡铂，当使用单小时暴露时，药物剂量增加了10倍。奈达铂、顺铂和卡铂与50%生长抑制（IC 50）相关的中位药物浓度分别为0.435、0.73和18.6 μ g/ml。顺铂和奈达铂均为10 μ g/ml，卡铂为100 μ g/ml，顺铂是最有效的药物，70%的肿瘤敏感（相对于对照平板，存活率小于或等于50%），分别对奈达铂和卡铂敏感45%和50%（P = 0.015，P = 0.074）。20例顺铂耐药的肿瘤中有6例（30%）同时对奈达铂和卡铂耐药。在剂量接近临床上可达到的药物浓度（由平均血浆浓度时间乘积定义）时，顺铂在未经化疗的宫颈癌中的体外细胞毒性似乎比卡铂或奈达铂更强。然而，奈达铂和卡铂也是具有相似活性的活性剂。由于药物敏感性的差异可能与剂量和给药方案的细微差异有关，并且奈达铂的药代动力学和安全性特征有利，因此需要进行奈达铂的临床试验。(C)北京：科学出版社.
Objective. To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients.Methods. Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma, Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [H-3]thymidine, Nedaplatin and cisplatin were tested at 1 and 10 mu g/ml dose levels while carboplatin was tested at 10 and 100 mu g/ml dose levels continuously, When single hour exposures were used, drug doses were increased by 10-fold.Results. The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 mu g/ml, respectively, At 10 mu g/ml for both cisplatin and nedaplatin and 100 mu g/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (less than or equal to 50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P = 0.015, P = 0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin,Conclusion. At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated. (C) 1998 Academic Press.