[Cis-diamminedichloroplatinum(II). A new antineoplastic agent derived from the group of heavy metal complexes (author's transl)]

Abstract

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.