[Phase I clinical study of antineoplastic agents]

Routinely, phase I clinical study starts with 1/10 of MELD10, provided dog does not produce toxicity. This is empirical method depend upon previous agents. In these days, many new agents appear to clinical study and some of them require so many steps to reach MTD. This is mainly depends upon differences of ADME between animals and human, which is possible to eliminate by pharmacokinetic studies. On the other hand, some of agents exceed MTD with initial dose of 1/10 MECL10. This is mainly due to difference of target organ sensitivity, and could be eliminated by assay of tissue enzyme activities. Another point should be emphasized is the existence of plasma peak level toxicity. This should be eliminated to perform preclinical study of LD10 by continuous infusion rather than iv bolus injection. Since some of new agents have DLF of neuro, hepato or cardiac toxicity rather than bone marrow, those would show quite different behaviors, therefore a special attention should be given for further studies.