[Phase I clinical study].

Abstract

The main purpose of the phase I clinical study is to define the tolerable doses in each various administration schedules depend upon by careful clinical observations and by pharmaco-kinetic, -dynamic studies. final goal of the phase I clinical study is to establish the safe, most reasonable administration schedules to perform further clinical studies, including phase II, III and possibly iv. In addition, it is quite reasonable to observe efficacy of the given agent if possible. The patients who are selected to receive the phase I clinical study should be fulfilled the followings: (1) Histological proof of malignancy; (2) No best available therapy regimen at present; (3) Maintain reasonably well organ functions which are suitable to observe side reactions (4) No hang-over reactions from previous therapy and; (5) Consent from patient himself or members of the family concerning the study. The set-up of the initial administration dose should be established from mouse and dog preclinical studies. Retrospective studies revealed reasonably safe and efficient to start from the most sensitive dose in 1/5 LD10 of mouse or 1/5 TDL of dog on the mg square meter basis. Above method is widely used at present and it is a potential replacement for the large animal species as a routine procedure. Dose escalation routinely proceeded using a double dose escalation procedure or modified Fibonacci procedures with minimal risk. It is permitted to escalate administration dose in the same patient under careful considerations. The new agent which has enough reliable clinical date in the abroad, the clinical study in this country would be simplified. The phase I clinical study should be performed in the well-equipped institutions under the supervision of capable investigators. The guide line of phase I clinical study would be revised whenever it is necessary.