[Present status of cisplatin (CDDP) analogues in Japan]

CDDP is an extremely active antineoplastic agent, yet has severe renal, upper GI and neurotoxicity. Therefore, extremely careful supportive care is necessary to administer this agent to patients. There are two ways to improve this agent. The first is to improve the activities of this agent, including widening the spectrum. The other is to reduce toxicity. By these two ways, the therapeutic window or efficacy of the agents will be increased. In these two factors in mind, 4 analogues, CBDCA, 254S, DWA 2114R and NK-121 are in clinical trials in Japan. These 4 agents are different from mother compound CDDP, that is the DLF is bone marrow depression with rather mild renal and upper GI toxicities with different degrees among analogues, compared with those of CDDP. Therefore, these 4 agents do not need hydration before and after the administration. The extensive studies of pharmacokinetics and dynamics are studied including plasma levels, protein bindings and urinary excretions. These above studies indicate some correlations in efficacy and toxicity, but not perfectly correlated. The experiences of the above 4 analogues are still too short to predict the possibility of neurotoxicity, however, it seems to be 4 analogues also neurotoxic. Above findings strongly suggests that the more clinical experiences are necessary to evaluate these analogues.