Lowis S P, Newell D R
Bristol Royal Hospital for Sick Children, U.K.
Eur J Cancer. 1996 Dec;32A(13):2291-7. doi: 10.1016/s0959-8049(96)00301-2.
Etoposide is one of the most important drugs available for the treatment of paediatric malignancies. Although there is evidence of schedule dependency for etoposide therapy in adults with small-cell lung cancer, the relevance of this observation to childhood cancers is uncertain. Prolonged parenteral or oral etoposide therapy has not yet shown a clear-cut advantage over intermittent treatment, and there are still no data to show that the administration of etoposide as a short intravenous (i.v.) daily infusion for 5 days does not represent acceptable therapy for primary disease. The pharmacokinetic variability seen with etoposide argues strongly for the use of pharmacologically guided dosing, and the introduction of etoposide phosphate will simplify both parenteral etoposide administration and the future evaluation of alternative etoposide schedules. Although the impact of molecular and cellular pharmacological investigations on the clinical use of etoposide has yet to be felt, the tools to perform these studies are now available and prospective trials can be designed. Such studies, performed in the setting of a pharmacologically guided trial to ensure control over pharmacokinetic variability, should identify the best way of treating children with etoposide.
依托泊苷是治疗儿童恶性肿瘤最重要的药物之一。尽管有证据表明在成人小细胞肺癌中依托泊苷治疗存在给药方案依赖性，但这一观察结果与儿童癌症的相关性尚不确定。延长的肠外或口服依托泊苷治疗尚未显示出比间歇性治疗有明显优势，而且仍没有数据表明将依托泊苷作为短程静脉每日输注5天的给药方式不适用于原发性疾病的治疗。依托泊苷所表现出的药代动力学变异性有力地支持了采用药理学指导给药，而磷酸依托泊苷的引入将简化肠外依托泊苷给药以及未来对替代依托泊苷给药方案的评估。尽管分子和细胞药理学研究对依托泊苷临床应用的影响尚未显现，但现在已具备开展这些研究的工具，并且可以设计前瞻性试验。在药理学指导试验的背景下进行此类研究，以确保控制药代动力学变异性，应该能够确定用依托泊苷治疗儿童的最佳方法。
