[Second-generation cisplatin analogs]

Since the introduction into clinical practice in 1972, cisplatin (CDDP) has assumed an important role in the treatment of various tumors such as testicular, ovarian or pulmonary cancer. Its toxicities include emesis, renal impairment, neuropathy, hearing loss and anemia. In clinical trials renal toxicity has been proved to be dose limiting factor. Thus the total number of courses which may be given is limited. For this reason second-generation CDDP analogues with reduced toxicity have been tried to develop and are reaching clinical testing. A number of studies have now been published relating the results of these trials. The best studied of these analogues is carboplatin (CBDCA, JM-8) which was noted to be less nephrotoxic, but more myelosuppressive than CDDP in preclinical study. Phase I trials have shown that CBDCA is relatively free of renal toxicity and that its dose limiting factor is myelosuppression, especially thrombocytopenia. In phase II trials CBDCA has been shown to be an active agent in advanced carcinomas of the ovary, head and neck, lung and urogenital organs. Similar results have been obtained in clinical trials of iproplatin (CHIP, JM-9) which is synthesized as an analogue of CDDP. Two other analogues developed in Japan have been evaluated to be active for various mouse tumors in preclinical studies. Phase I trials of these agents is now ongoing.