EFFECT OF DRUG SCHEDULING ON THE ANTITUMOR-ACTIVITY AND BONE-MARROW TOXICITY OF TAUROMUSTINE (TCNU)

The effect of administering divided dose schedules of TCNU was examine d against the murine adenocarcinomas of the colon, MAC 13 and MAC 26, and the Lewis lung tumour and drug metabolism was examined in the diff erent tumour bearing mouse strains. Bone marrow toxicity of the dose s chedules was assessed using a spleen colony forming unit assay. In add ition, the effect of drug scheduling was investigated in a Phase I cli nical setting. Differing levels of efficacy of the divided dose schedu les were observed in the different murine tumour models. A therapeutic advantage was found in the Lewis lung tumour whereas none was found i n either MAC 13 or MAC 26 tumours. The extent and nature of TCNU metab olism varied between the mouse strains which might contribute to the d iffering activity-toxicity patterns obtained. The results suggest that divided dose scheduling of TCNU might only be useful in selected pati ents.