Osieka R, Schmidt C G
Klin Wochenschr. 1979 Dec 3;57(23):1249-58. doi: 10.1007/BF01492980.
Platinum coordination complexes represent a new class of antineoplastic agents among which only cis-diamminedichloroplatinum(II) (cis-DDP) has undergone extensive clinical trials. Cis-DDP and some of its congeners share the potential to form DNA-crosslinks with the group of bifunctional alkylating agents, yet cross-resistance is incomplete. The prominent dose-limiting nephrotoxicity can be effectively circumvented by forced diuresis. Cis-DDP not only displays outstanding activity against non-seminomatous testicular cancer but also has a broad spectrum of clinical activity. It ranks very high in activity against bladder cancer and head and neck tumors. Since myelosuppression by cis-DDP is mild, it combines well with other antineoplastic agents. Synergism has been experimentally shown for cyclophosphamide and several other antineoplastic agents. For testicular cancer combination chemotherapy including cis-DDP has become accepted treatment. The simple geometry of platinum coordination complexes allows substitutions of leaving and remaining ligands with anorganic or organic moieties thus altering pharmakokinetic, antineoplastic, and toxic properties in comparison to the parent compound. Mechanism of action, pharmacology, and clinical use of cis-DDP as well as of potentially useful congeners are discussed in this review, since cis-DDP is expected to be available for general use in medical oncology in the near future.
铂配位络合物代表了一类新型抗肿瘤药物，其中只有顺二氯二氨铂（II）（顺铂）进行了广泛的临床试验。顺铂及其一些同类物具有与双功能烷化剂组形成DNA交联的潜力，但交叉耐药并不完全。通过强制利尿可以有效规避突出的剂量限制性肾毒性。顺铂不仅对非精原性睾丸癌表现出出色的活性，而且具有广泛的临床活性。它对膀胱癌和头颈肿瘤的活性非常高。由于顺铂引起的骨髓抑制较轻，它与其他抗肿瘤药物联合使用效果良好。实验表明顺铂与环磷酰胺和其他几种抗肿瘤药物具有协同作用。对于包括顺铂在内的睾丸癌联合化疗已成为公认的治疗方法。铂配位络合物简单的几何结构允许用无机或有机部分取代离去和残留的配体，因此与母体化合物相比，其药代动力学、抗肿瘤和毒性特性会发生改变。本文综述了顺铂以及潜在有用的同类物的作用机制、药理学和临床应用，因为预计顺铂在不久的将来可用于医学肿瘤学的一般治疗。
