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Effect of drug scheduling on the antitumor-activity and bone-marrow toxicity of tauromustine (tcnu)
A Matthew1, P Christensson, J Seidegard
1LUND UNIV,WALLENBERG LAB,DEPT MOLEC ECOGENET,S-22101 LUND,SWEDEN. ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY 14263.
Abstract:
The effect of administering divided dose schedules of TCNU was examined against the murine adenocarcinomas of the colon, MAC 13 and MAC 26, and the Lewis lung tumour and drug metabolism was examined in the different tumour bearing mouse strains. Bone marrow toxicity of the dose schedules was assessed using a spleen colony forming unit assay. In addition, the effect of drug scheduling was investigated in a Phase I clinical setting. Differing levels of efficacy of the divided dose schedules were observed in the different murine tumour models. A therapeutic advantage was found in the Lewis lung tumour whereas none was found in either MAC 13 or MAC 26 tumours. The extent and nature of TCNU metabolism varied between the mouse strains which might contribute to the differing activity-toxicity patterns obtained. The results suggest that divided dose scheduling of TCNU might only be useful in selected patients.
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