Cisplatin — Past, Present and Future

Abstract

Cisplatin is a triumph which elucidates many aspects of clinical cancer research in general and drug development research in particular. As is well known cisplatin was discovered initially by a brilliantly intuitive serendipitous observation by Dr. Barrett Rosenberg.⁽¹⁾ The critical step in bringing the drug to clinical trial was the observation by the NCI drug development program that the compound was highly effective in its experimental tumor systems. It was this experimental activity which led the NCI to develop the drug for clinical study and ultimately file an Investigational New Drug application (IND) with the Food and Drug Administration.⁽²⁾ It is worth noting that the first patient treated with the drug was at the Wadley Institute in Dallas, without an IND, and at initially very high doses. In the NCI sponsored trials it was initially observed that the drug was active and toxic to the kidney. Some early views were that the renal toxicity would obviate general widespread use of the drug. The potential value of the drug was so obvious however that experimentation eventually found, through hydration, a mechanism to significantly ameliorate the renal toxicity. With the ability to circumvent renal toxicity, higher doses of the drug could be administered and a wide range of solid tumor activity was uncovered. This activity brought the drug into the disease-oriented strategies of the national cancer programs clinical research thrust. For example the activity in testicular cancer, first observed at Roswell-Park Memorial Institute,^(3–4) by the group under James Hollands leadership, had significant impact on the development of curative chemotherapy for this disease in its metastatic phase (Figure 1). Golbey and associates first combined cisplatin with vinblastine, bleomycin and actinomycin D after the important observation by Samuels⁽⁶⁾ of the great activity of high dose vinblastine combined with bleomycin. Einhorn⁽⁷⁾ achieved the most successful, and widely accepted results, combining cisplatin with high dose vinblastine and bleomycin, initially with BCG.