In the course of examining the effect of electric fields on the growth of Escherichia coli cells, a biological activity of platinum compounds was uncovered that led to the development of some of the most widely used anticancer drugs today. 1, 2 Compounds formed by reaction of platinum from the electrodes with ammonium chloride in the buffer stopped cell division and induced filamentous growth in the bacteria. Subsequent testing of these compounds in mice revealed antitumor activity. 2, 3 One of the more successful compounds, cis-diamminedichloroplatinum (II), or cisplatin, had been known since 1845, 4, 5 but not until 1970 was its antitumor activity established. 2, 3, 6 Since this serendipitous discovery, cisplatin has been used to treat a variety of human malignancies.

Early clinical trials with cisplatin were promising, the one major drawback being severe renal toxicity that was ultimately overcome through hydration therapy and diuresis. 7 Cisplatin was approved by the FDA in 1978, and the cure rate for testicular cancer is now greater than 90% when tumors are promptly diagnosed. 8 Cisplatin is also used to treat other kinds of malignancies, including ovarian, cervical, head and neck, esophageal, and nonsmall cell lung cancer. 9 The cisplatin treatment regimen generally involves a series of intravenous injections administered every 3-4 weeks at a dose of 50-120 mg/m2. 9 Despite the great success at treating certain kinds of cancer, the drug does have some limitations. There are several side effects, and both intrinsic and acquired resistance limit the organotropic profile of the drug. Over the years, various platinum complexes, some of which are shown in Figure 1, have been studied in an attempt to overcome these problems. Many of the compounds exhibiting antitumor activity have had two cis-amine ligands, and trans-diamminedichloroplatinum (II)(trans-DDP), the geometric isomer of cisplatin, is clinically ineffective. Carboplatin, cis-diammine-1, 1′-cyclobutane dicarboxylate platinum-(II), has reduced toxicity but is cross-resistant with cisplatin. 10 Oxaliplatin, trans-L-diaminocyclohexaneoxalatoplatinum (II), displayed a lack of crossresistance and has been used to treat colorectal cancer. 11, 12 Orally active platinum (IV) compounds that would broaden treatment conditions are also in development. 13 In addition, recent work suggests that there may be some biologically active trans platinum compounds, including platinum (II) complexes with planar ligands, 14-16 platinum (II) iminoether compounds, 17, 18 and trans-ammine (amine) platinum (IV) compounds. 19-21 Over 3000 cisplatin analogues have been tested, 22 with 28 platinum compounds, selected for some of the activities described above, having entered clinical trials. 10 Unfortunately, most of these drug candidates have encountered difficulties in the clinic, perhaps due to the fact that a specific cellular target or mechanism was not used as the basis for drug design. It is estimated that more than 10 000 compounds need to be screened in order to obtain a new, effective anticancer drug. 23 The development of new antitumor platinum compounds will not be further addressed in this review because it is covered elsewhere in this issue.