Biologic and clinical developments of cisplatin combined with radiation: concepts, utility, projections for new trials, and the emergence of carboplatin.
Biologic and clinical developments of cisplatin combined with radiation: concepts, utility, projections for new trials, and the emergence of carboplatin.
复制标题
DOI：
--
复制
发表时间：
1989
影响因子：
4
通讯作者：
C. Coughlin;R. Richmond
中科院分区：
文献类型：
--
作者：
C. Coughlin;R. Richmond
对照实验表明，不止一种机制导致顺铂增强辐射诱导的细胞杀伤作用，并且这种增强作用在不同细胞类型中的表达并不统一。尚未建立使用顺铂和放射治疗的临床试验设计的坚实研究基础。与实验指导的这种缺陷相一致，独立临床研究者开发了一系列治疗策略，对各种肿瘤类型应用不同剂量和顺序的顺铂和放射。与现有放射生物学信息进行比较，评估可判断感知生存益处的顺铂和放射治疗相结合的临床研究结果。目前的临床和放射生物学结果都得出了类似的结论。对单独顺铂的细胞毒性作用相对敏感的细胞最好考虑与放射联合治疗。大量且不频繁地单独施用顺铂，而不是少量且频繁地单独施用，与放射一起使用可以更好地增强治疗效果。尽管感知疗效来自于这两种方式的相当灵活的整合，但在接近放疗的时间施用顺铂对于治疗反应是最好的。不可能知道临床疗效是否来自辐射增强，而不是两种方式某种程度的相加。尽管如此，在治疗设计中预测可能导致顺铂增强辐射的策略仍然是有用的。确定了顺铂增强辐射诱导的细胞杀伤的两种一般机制。一种增强机制是自由基介导的，在顺铂的单电子还原后至少部分地导致活性放射解物质，并且在组织培养中比在哺乳动物细胞中更容易在细菌细胞中表达。第二种增强机制本质上是生物化学的，涉及顺铂以抑制辐射引起的损伤恢复的方式对细胞成分产生影响，并且可能更适用于含氧哺乳动物细胞而不是细菌细胞的增强。后一种机制并未得到文献的普遍支持。然而，目前需要证实的一个统一假设是，顺铂增强辐射的生化机制在对顺铂的细胞毒性作用本质上敏感的含氧哺乳动物细胞中起作用。这一假设表面上适用于对顺铂化疗有反应的肿瘤细胞。（摘要截断为 400 字）
Controlled experiments have shown that more than one mechanism leads to the potentiation of radiation-induced cell killing by cisplatin, and that this potentiation is not uniformly expressed among different cell types. A firm investigative base for the design of clinical trials using cisplatin and radiation has not been established. Coincident with this deficiency of experimental guidance, the independent clinical investigator has developed an array of therapeutic strategies applying different doses and sequences of cisplatin and radiation to a variety of tumor types. Results of clinical studies integrating cisplatin and radiation that can be judged for perceived survival benefit are evaluated in comparison with existing radiobiologic information. Both the clinical and radiobiologic results lead to similar conclusions at this time. Cells that are relatively sensitive to the cytotoxic action of cisplatin alone would best be considered for combined treatment with radiation. Large and infrequent, rather than small and frequent, individual administrations of cisplatin are better used with radiation for enhanced therapeutic effectiveness. Administration of cisplatin close in time to radiation is best for therapeutic response, although perceived efficacy follows from rather flexible integrations of these two modalities. It is not possible to know if clinical efficacy results from radiation potentiation as opposed to some degree of additivity of the two modalities. It is nonetheless useful to anticipate strategies that might lead to radiation potentiation by cisplatin in therapeutic designs. Two general mechanisms by which cisplatin potentiates radiation-induced cell killing are identified. One mechanism of potentiation is free radical-mediated, at least in part leads to an active radiolytic species following one-electron reduction of cisplatin, and is more readily expressed with bacterial cells than with mammalian cells in tissue culture. A second mechanism of potentiation is biochemical in nature, involves an effect of cisplatin on cellular components in ways that inhibit the recovery of radiation-induced damage, and likely applies more to the potentiation of oxic mammalian cells than bacterial cells. The latter mechanism is not universally supported in the literature. However, a unifying hypothesis, and one in need of confirmation at this time, is that the biochemical mechanism of radiation potentiation by cisplatin operates in oxic mammalian cells that are inherently sensitive to the cytotoxic action of cisplatin. This hypothesis ostensibly applies to tumor cells that are responsive to chemotherapy with cisplatin.(ABSTRACT TRUNCATED AT 400 WORDS)