Foster B J, Harding B J, Wolpert-DeFilippes M K, Rubinstein L Y, Clagett-Carr K, Leyland-Jones B
Investigational Drug Branch, National Cancer Institute, Bethesda, Maryland.
Cancer Chemother Pharmacol. 1990;25(6):395-404. doi: 10.1007/BF00686049.
The antitumor agent cisplatin has a broad antitumor spectrum and has been incorporated into regimens that are curative for some malignant diseases. However, one of the major limitations to its clinical usefulness is the incidence of severe toxicities involving several major organ systems. Therefore, much enthusiasm has been generated for the development of cisplatin analogs that demonstrate an improved therapeutic index in some preclinical models. The two most promising analogs are CBDCA (carboplatin) and CHIP (iproplatin). The preclinical and early clinical trial results have demonstrated that these two compounds show activity in cisplatin-responsive tumors. The preclinical background providing the rationale for the clinical development of these two analogs is described. We suggest a means of screening for each analog's clinical antitumor activity and determining the analogs' utility against specific malignant diseases compared with that of the parent compound or standard treatment.
抗肿瘤药物顺铂具有广泛的抗肿瘤谱，已被纳入一些可治愈某些恶性疾病的治疗方案中。然而，其临床应用的主要局限性之一是涉及多个主要器官系统的严重毒性的发生率。因此，人们对开发在一些临床前模型中显示出改善的治疗指数的顺铂类似物产生了极大的热情。两种最有前景的类似物是卡铂（CBDCA）和异丙铂（CHIP）。临床前和早期临床试验结果表明，这两种化合物在对顺铂敏感的肿瘤中显示出活性。本文描述了为这两种类似物的临床开发提供理论依据的临床前背景。我们提出了一种筛选每种类似物临床抗肿瘤活性的方法，并确定与母体化合物或标准治疗相比，这些类似物对特定恶性疾病的效用。
