Action of Platinum Antitumour Drugs

Abstract

Studies leading to the present understanding of the biological activities of platinum coordination complexes, and to the use of such compounds in cancer chemotherapy, began in the 1960s, when Rosenberg and co-workers discovered that certain electrolysis products generated from platinum electrodes passing current through growth medium selectively inhibited cell division in bacteria (Rosenberg et al., 1965, 1967). Several years later, the same group reported that certain platinum coordination complexes displayed significant antitumour activity in vivo (Rosenberg et al., 1969). The discovery of the antitumour activity of platinum coordination complexes eventually led to the introduction of one compound, cis-dichlorodiamine platinum (II) (cis-DDP, or cisplatin), into therapeutic trials in the treatment of human malignancy. While the initial trials demonstrated the activity of the drug against human tumours, renal toxicity appeared to be a serious limitation to the use of the compound (Gottlieb and Drewinko, 1975), since it occurred at therapeutic doses and was only partially reversible. However, clinical oncologists continued to explore ways of administering the drug, and it was found that fluid administration or induction of diuresis allowed oncologists to avoid prohibitive nephrotoxicity during cisplatin therapy (Einhorn and Donohue, 1977; Hayes et al., 1977). The agent was found to enhance long-term survival significantly in combination therapy of testicular cancer (Einhorn and Williams, 1980) (table 1), and to be active in the treatment of ovarian carcinoma and squamous cell carcinoma of the head and neck (for a review of the clinical activity of cis — DDP, see Prestayko et al., 1979).